Affinage

ITGB2

Integrin beta-2 · UniProt P05107

Round 2 corrected
Length
769 aa
Mass
84.8 kDa
Annotated
2026-04-28
130 papers in source corpus 67 papers cited in narrative 66 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGB2 (CD18) encodes the common beta-2 integrin subunit that heterodimerizes with alpha subunits CD11a, CD11b, and CD11c to form LFA-1, Mac-1, and p150,95, respectively, constituting the principal leukocyte adhesion receptor family that mediates firm arrest, transendothelial migration, phagocytosis, and immune cell–cell communication (PMID:3028646, PMID:3594570). These heterodimers undergo bidirectional conformational signaling—inside-out activation driven by Rap1, talin-1, Kindlin-3, and cytohesin-1 separates the alpha/beta cytoplasmic tails to expose high-affinity ligand-binding states, while outside-in signaling through Src/Syk kinases controls effector responses including elastase release, LC3-associated phagocytosis, extracellular vesicle generation, and neutrophil survival (PMID:14500982, PMID:16872848, PMID:8706128, PMID:29923444). Mac-1 binds an exceptionally diverse ligand repertoire—ICAM-1, fibrinogen, iC3b, GPIbα, plasminogen, ISG15, LL-37, and others—primarily through the alpha-chain I-domain, with a lectin-like domain modulating affinity and pathogen recognition (PMID:7679388, PMID:10899906, PMID:29100055, PMID:27990411). Loss-of-function mutations in ITGB2 cause Leukocyte Adhesion Deficiency (LAD), characterized by impaired surface expression of all beta-2 integrins, abolished leukocyte adhesion, and recurrent infections, correctable by retroviral gene transfer (PMID:3594570, PMID:1972597).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1987 High

    Cloning of ITGB2 established it as the shared beta subunit of the leukocyte integrin family and identified heterogeneous mutations as the molecular basis of Leukocyte Adhesion Deficiency, resolving a decades-old clinical syndrome at the gene level.

    Evidence cDNA cloning, peptide sequencing, Northern/Southern blots, family studies, immunoprecipitation in LAD patient cells

    PMID:3028646 PMID:3594570

    Open questions at the time
    • Precise structure–function relationship of individual mutations unknown
    • Regulatory elements controlling ITGB2 expression uncharacterized
  2. 1988 High

    Identification of Mac-1 as an inducible fibrinogen receptor and demonstration of pre-formed intracellular granule pools explained how neutrophils rapidly amplify CD18 surface expression without new protein synthesis.

    Evidence Cell adhesion/binding assays with mAb inhibition, subcellular Percoll fractionation and lectin immunoblot in neutrophils

    PMID:2903896 PMID:3053736

    Open questions at the time
    • Granule targeting signals for Mac-1 not defined
    • Mechanism coupling degranulation to membrane insertion unclear
  3. 1990 High

    Discovery that ICAM-1 is a counter-receptor for both LFA-1 and Mac-1, and that LAD point mutations (R593C, K196T) prevent surface expression, defined the key ligand–receptor axis and linked specific residues to disease pathogenesis; retroviral gene correction rescued adhesion in LAD cells, providing proof-of-concept for gene therapy.

    Evidence Purified protein binding, transfectant adhesion assays, COS cell expression of mutant CD18, retroviral transduction of LAD lymphocytes

    PMID:1968911 PMID:1972597 PMID:1980124

    Open questions at the time
    • Three-dimensional structure of CD18 ectodomain unknown
    • Efficiency and safety of gene correction in vivo untested
  4. 1993 High

    Mapping the alpha-chain I-domain as the principal binding site for iC3b, fibrinogen, ICAM-1, and homotypic adhesion ligands unified diverse Mac-1 functions under a single structural motif, while CD18-hypomorphic mice confirmed the integrin's essential role in inflammatory cell recruitment in vivo.

    Evidence Alpha subunit chimeras with mAb panel mapping; gene-targeted CD18-hypomorphic mice in peritonitis and transplant models

    PMID:7679388 PMID:8101543

    Open questions at the time
    • Atomic details of I-domain–ligand contacts unresolved
    • Relative contributions of LFA-1 vs Mac-1 in different tissues not dissected
  5. 1996 High

    Identification of cytohesin-1 as a direct CD18 cytoplasmic tail interactor that activates LFA-1 adhesion revealed the first intracellular effector of inside-out integrin signaling specific to the beta-2 chain.

    Evidence Protein interaction assay, overexpression/dominant-negative experiments in Jurkat T cells, ICAM-1 adhesion

    PMID:8706128

    Open questions at the time
    • Cytohesin-1 binding site on CD18 not mapped at residue level
    • Relationship to other inside-out regulators (talin, Kindlin-3) unresolved
  6. 2000 High

    Discovery that platelet GPIbα is a Mac-1 counter-receptor bridged leukocyte integrin biology to hemostasis, demonstrating that Mac-1–GPIbα interaction underlies neutrophil–platelet adhesion and subsequent thrombotic signaling.

    Evidence Adhesion assays with Mac-1 KO neutrophils, GPIbα domain mapping, mocarhagin cleavage, flow-based assays

    PMID:10899906

    Open questions at the time
    • Structural basis of I-domain–GPIbα recognition not determined
    • In vivo thrombotic contribution not yet quantified at this stage
  7. 2003 High

    FRET measurements in living cells demonstrated that alpha/beta cytoplasmic tail separation is the physical switch for both inside-out and outside-in LFA-1 signaling, providing a unifying biophysical mechanism for bidirectional integrin activation.

    Evidence CFP/YFP-tagged cytoplasmic domain FRET in living cells under inside-out (TCR) and outside-in (ICAM-1) activation

    PMID:14500982

    Open questions at the time
    • Whether all beta-2 heterodimers use identical tail separation geometry unknown
    • Connection between tail separation and downstream kinase activation not directly shown
  8. 2006 High

    Epistatic analysis across Mac-1, Hck, Syk, and elastase knockout mice established the complete outside-in signaling cascade from complement C3 recognition through Src/Syk kinases to elastase release causing hemorrhage and thrombosis, defining the first full pathway from integrin engagement to tissue injury.

    Evidence Five genetic KO mice (Mac-1, C3, Hck, Syk, elastase), bone marrow transfers, in vitro elastase release

    PMID:16872848

    Open questions at the time
    • Intermediate signaling steps between Syk and elastase secretion uncharacterized
    • Whether this pathway operates identically in human neutrophils untested
  9. 2006 High

    Talin-1 was shown to be required for TCR-triggered LFA-1 affinity and avidity, and LFA-1 nanoclusters were visualized as dynamic adhesion units, establishing that integrin avidity regulation involves hierarchical spatial organization from nanocluster to macrocluster scales.

    Evidence siRNA knockdown of talin-1 with ICAM-1 adhesion/activation readouts; near-field optical microscopy of LFA-1 nanoclusters on monocytes

    PMID:16855029 PMID:17114441

    Open questions at the time
    • How Kindlin-3 cooperates with talin-1 at the nanocluster level unresolved
    • Nanocluster composition beyond LFA-1 and talin not defined
  10. 2012 High

    Integrating intravital microscopy with conformation-specific antibodies distinguished two LFA-1 activation states—extended/closed-headpiece for slow rolling (via PSGL-1) and extended/open-headpiece for firm arrest (via CXCR2)—resolving how a single integrin generates distinct adhesive behaviors through differential inside-out signaling involving talin-1 and Kindlin-3.

    Evidence Intravital microscopy, flow chambers, conformation-specific mAbs in neutrophils, talin-1/Kindlin-3 functional studies

    PMID:22701459

    Open questions at the time
    • Structural intermediates between closed and open headpiece not captured crystallographically in the beta-2 context
    • Quantitative contribution of each conformational state to in vivo extravasation not established
  11. 2017 High

    ISG15 was identified as a new LFA-1 ligand that signals IFN-γ secretion through Src-family kinases, while Mac-1–GPIbα interaction was shown to regulate thrombosis via Foxp1, expanding CD18 functions to innate cytokine signaling and transcriptional regulation of hemostasis.

    Evidence Direct I-domain binding of ISG15, CD11a KO splenocytes, SFK inhibition; Mac-1 KI mice with GPIbα-binding site mutation, adoptive transfer, arterial injury models

    PMID:28555620 PMID:29100055

    Open questions at the time
    • ISG15–LFA-1 structural interface unresolved
    • Foxp1 target genes mediating the thrombotic program not identified
  12. 2018 High

    Mac-1 was identified as the initiating receptor for LC3-associated phagocytosis (LAP) of Listeria in tissue macrophages, distinguishing LAP from canonical autophagy and assigning a specific integrin entry point to this antimicrobial pathway.

    Evidence Mac-1 KO mice in in vivo Listeria infection model, genetic dissection of LAP vs canonical autophagy

    PMID:29923444

    Open questions at the time
    • How Mac-1 engagement triggers Rubicon/VPS34 LAP machinery not defined
    • Whether other beta-2 heterodimers can initiate LAP unknown
  13. 2020 High

    Tensile force on LFA-1 was shown to assemble a Kindlin-3/RACK1/Orai1 mechanotransduction complex that directs ER translocation and Ca²⁺ influx, providing a molecular mechanism linking integrin mechanosensing to neutrophil polarization and migration.

    Evidence Live cell imaging, shear stress manipulation, Ca²⁺ flux assays, Kindlin-3/RACK1 interaction studies in neutrophils

    PMID:32531836

    Open questions at the time
    • Whether this mechanotransduction complex operates in lymphocytes unknown
    • Direct force measurement on single LFA-1 bonds not performed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full atomic structure of intact beta-2 integrin heterodimers in membrane context, how distinct alpha/beta pairings generate divergent downstream signaling outputs from the same CD18 cytoplasmic domain, the precise mechanism linking Mac-1 engagement to LAP machinery, and whether CD18-targeted therapies can selectively modulate specific heterodimer functions without global immunosuppression.
  • No full-length beta-2 integrin cryo-EM structure in lipid bilayer
  • Mechanism of heterodimer-specific signaling selectivity unknown
  • Therapeutic selectivity between LFA-1 and Mac-1 functions unachieved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 7 GO:0008092 cytoskeletal protein binding 4 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 7 GO:0031410 cytoplasmic vesicle 4
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 7 R-HSA-1500931 Cell-Cell communication 6 R-HSA-1474244 Extracellular matrix organization 5 R-HSA-109582 Hemostasis 3 R-HSA-9612973 Autophagy 1
Partners
CYTH1FERMT3GP1BAICAM1ITGALITGAMITGAXTLN1
Complex memberships
LFA-1 (CD11a/CD18)Mac-1 (CD11b/CD18)p150,95 (CD11c/CD18)

Evidence

Reading pass · 66 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 The CD18 (ITGB2) gene encodes the common beta subunit shared by LFA-1, Mac-1, and p150,95; heterogeneous mutations in the beta subunit gene are the primary defect in Leukocyte Adhesion Deficiency (LAD), with five distinct mutant beta subunit phenotypes identified, all failing to associate with the LFA-1 alpha subunit. cDNA cloning, Northern blot, family studies, immunoprecipitation Cell High 3594570
1987 CD18 (ITGB2) cDNA was cloned; the deduced 769-amino-acid sequence defines a cysteine-rich integral membrane protein with 45% homology to the integrin beta subunit, establishing the leukocyte integrin beta chain as part of a supergene family with matrix receptors. cDNA cloning, peptide sequencing, Northern blot, Southern blot Cell High 3028646
1988 Mac-1 (CD11b/CD18) functions as an inducible receptor for fibrinogen on monocytes and myeloid cells; fibrinogen binding is distinct from RGD-directed receptors and is activated by agonists that induce cytosolic Ca2+ transients during myeloid differentiation. Cell adhesion assays, mAb inhibition, flow cytometry, cell stimulation assays The Journal of cell biology High 3053736
1988 Mac-1 (CD11b/CD18) is stored in intracellular granule pools in neutrophils; chemotactic stimulation (fMLP) mobilizes a pre-gamma granule pool to the plasma membrane, causing a 4-8-fold increase in surface Mac-1 without requiring protein synthesis. Lectin immunoblot, subcellular fractionation on Percoll gradients, flow cytometry Journal of leukocyte biology High 2903896
1989 CD11b/CD18 (Mac-1) exists in functionally distinct membrane populations: a mobile pool mediating C3bi rosetting and an immobile, cytoskeleton-associated pool required for phagocytosis. Cytochalasin treatment abolishes apical CD11b/18 and phagocytosis, demonstrating microfilament dependence of the phagocytic pool. mAb inhibition of phagocytosis vs. rosetting, cytochalasin treatment, flow cytometry, adherence assays Journal of immunology High 2538507
1989 CD11a/CD18 (LFA-1) mediates neutrophil adhesion to endothelial ICAM-1, while CD11b/CD18 (Mac-1) mediates adhesion to a distinct, non-ICAM-1 ligand on endothelial cells; each contributes approximately equally (~50%) to total PMN adhesion to unstimulated endothelium. mAb blocking studies, ICAM-1 surface downmodulation assay, PMN adhesion assays Journal of immunology High 2809204
1990 Mac-1 (CD11b/CD18) binds fibrinogen through a unique recognition site in the D fragment (~30 kDa plasmic fragment, D30) that lacks RGD sequences and the gamma-chain C-terminal dodecapeptide, establishing a novel fibrinogen-binding site distinct from all other known integrin-fibrinogen interactions. Proteolytic fragmentation of fibrinogen, 125I-binding assays, mAb inhibition, microsequence analysis The Journal of biological chemistry High 1973686
1990 Point mutations in CD18 (Arg593→Cys and Lys196→Thr) cause impaired cell surface expression of CD18 in a LAD patient; each mutant allele prevents CD18 from reaching the cell surface in transfected COS cells, identifying conserved residues critical for CD18 expression. cDNA sequencing, COS cell transfection, flow cytometry The Journal of clinical investigation High 1968911
1990 The genetic and functional defects of LAD lymphocytes (lacking CD18) were corrected by retrovirus-mediated transduction of a functional CD18 gene, restoring LFA-1-dependent adhesive function. Retroviral gene transfer, flow cytometry, LFA-1-dependent adhesion assays Science High 1972597
1990 ICAM-1 is a counter-receptor for Mac-1 (CD11b/CD18); purified Mac-1 binds ICAM-1-transfected cells and vice versa, and this interaction contributes to neutrophil-endothelial adhesion in a stimulation-dependent manner. Purified protein binding assays, transfected cell adhesion assays, mAb blocking, two-color conjugate experiments The Journal of cell biology High 1980124
1991 Mn2+ ions occupy divalent cation binding sites on CD11b/CD18 and constitutively induce maximal ligand binding affinity (up to 10-fold increase), bypassing normal cell-activation requirements; this is associated with expression of activation-dependent neoepitopes recognized by mAb 7E3. Cell adhesion assays, Scatchard analysis of receptor-ligand binding, flow cytometry with activation-specific mAbs Journal of immunology High 1890307
1991 CD40 signaling in B cells activates CD18-dependent adhesion; CD40 ligation induces increased surface expression of ICAM-1 and activates the CD11a/CD18 (LFA-1)-ICAM adhesion system in an energy-, protein synthesis-, and mRNA synthesis-dependent manner. Homotypic aggregation assays, mAb blocking, CD40-transfected cell lines, metabolic inhibitors Journal of immunology High 1706378
1992 The CD18 promoter was identified and characterized; it lacks TATA and CAAT boxes but contains Sp1 binding sites and T(G/C)AC(C/A) boxes (putative RAR binding sites). CD18 is transcriptionally regulated during TPA-induced monocytic differentiation, with AP-1 and PU.1 binding sites identified. Primer extension, RNase protection, S1 nuclease, reporter gene (luciferase/growth hormone) transfection assays, nuclear run-on Blood High 1346252 1350225
1993 The I domain on the CD11b alpha chain of Mac-1 is the major recognition site for four distinct ligands: iC3b, fibrinogen, ICAM-1, and the neutrophil homotypic adhesion counter-receptor; the binding sites are overlapping but not identical as revealed by discrete inhibitory mAb patterns. Alpha subunit chimeras of Mac-1 and p150,95, mAb panel binding studies, ligand binding inhibition assays The Journal of cell biology High 7679388
1993 Gene targeting in mice introduced a hypomorphic CD18 mutation (insertion mutation activating cryptic promoter) producing 2-16% normal CD18 expression; CD18-mutant mice show impaired inflammatory response to chemical peritonitis and delayed cardiac transplant rejection, establishing CD18 as essential for integrin-mediated inflammatory cell adhesion in vivo. Gene targeting, flow cytometry, peritonitis model, cardiac transplant model Journal of immunology High 8101543
1993 Phospholipase A2 (PLA2) is a key regulator of CD11b/CD18 (Mac-1) surface expression in neutrophils; selective PLA2 inhibitors (manoalide, scalaradial) block Mac-1 upregulation from intracellular granules in response to diverse stimuli (fMLP, IL-8, TNF-α, PMA, PAF), independent of cyclooxygenase or lipoxygenase pathways. Flow cytometry, [3H]arachidonic acid release assays, granule secretion assays, pharmacological inhibition Journal of immunology High 8228253
1995 L-selectin cross-linking on neutrophils signals activation of Mac-1 (CD11b/CD18)-dependent adhesion; this involves increased surface CD18, expression of activation-dependent epitope (mAb24), and promotion of neutrophil transmigration across endothelium. Flow cytometry-based bead capture assay, mAb cross-linking with F(ab')2 fragments, transendothelial migration assay Journal of immunology High 7543524
1995 CD11c/CD18 (p150,95) functions as a transmembrane signaling receptor for LPS; CHO cells transfected with CD11c/CD18 acquire serum-independent NF-κB activation in response to LPS and Gram-negative bacteria, independently of CD14, establishing CD11c/CD18 as a signal-transducing LPS receptor. Heterologous CHO cell transfection, NF-κB reporter assay, LPS stimulation The Journal of experimental medicine High 7535339
1995 LFA-1 (CD11a/CD18) exhibits inside-out and outside-in bidirectional signaling; inside-out signaling from T cell activation regulates LFA-1 adhesive avidity via cytoskeletal interactions, while outside-in signaling through LFA-1 stimulates intracellular processes. Adhesion assays, cytoskeletal perturbation, signaling readouts in T cells and B-CLL cells Immunology today Medium 7576051
1995 A peptide derived from ICAM-2 binds directly to purified CD11b/CD18 and CD11c/CD18, and stimulates their avidity for ICAM-1, fibrinogen, and iC3b in monocytic cell lines, demonstrating that ICAM-2 can act as an activating ligand for beta2 integrins beyond LFA-1. Direct binding to purified integrins, cell aggregation assays, fibrinogen/iC3b adhesion assays The Journal of cell biology High 7744962
1996 Cytohesin-1 specifically interacts with the intracellular portion of the CD18 (beta2) cytoplasmic domain; overexpression of cytohesin-1 or its SEC7 domain induces beta2 integrin-dependent LFA-1 binding to ICAM-1, while the isolated PH domain inhibits TCR-stimulated adhesion. Protein interaction studies, overexpression in Jurkat cells, ICAM-1 adhesion assays Cell High 8706128
1998 CD18 functions as the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin (LtxA); chimeric beta2-integrin experiments demonstrated that the cysteine-rich EGF-like domains 2, 3, and 4 of the CD18 extracellular region confer species-specific susceptibility to LtxA-induced cytotoxicity. Chimeric beta2-integrin transfection into resistant cell line, LtxA cytotoxicity assays Infection and immunity High 17635865
1998 Interaction of Candida albicans with CD11b/CD18: the I domain is the primary binding site; the lectin-like domain modulates I domain function; a single point mutation at Ser138 of CD18 exerts a dominant negative effect on the CD11b/CD18-C. albicans interaction, abolishing binding even when CD11b alone binds well. Site-directed mutagenesis of CD18, transfection studies, binding assays with C. albicans Journal of immunology High 9834106
1998 CD11/CD18 and CD14 utilize a common LPS signal transduction pathway; a cytoplasmic deletion mutant of CD11/CD18 retains the ability to activate NF-κB via LPS in CHO cells, arguing that CD11/CD18 utilizes an associated signal transducer rather than its own cytoplasmic domain. CHO cell transfection with deletion mutants, NF-κB reporter assays, lipid A analogue specificity testing Journal of immunology High 9820516
1999 Salmonella typhimurium is transported from the gastrointestinal tract to bloodstream by CD18-expressing phagocytes; CD18-deficient mice are resistant to systemic dissemination, establishing CD18 as required for Salmonella's phagocyte-dependent extraintestinal spread. CD18-deficient mouse model, bacterial dissemination assays, oral infection experiments Nature High 10548107
1999 A missense mutation Cys36Ser in the ITGB2 gene causes canine LAD; this conserved cysteine residue in all beta integrins likely forms a disulfide bond, and the mutant CD18 fails to form heterodimers with CD11 subunits at normal levels when expressed by retroviral transduction in human LAD cells. DNA sequencing, retroviral transduction, flow cytometry of CD11/CD18 expression Genomics High 10512685
1999 Heparin binds directly to Mac-1 (CD11b/CD18) on PMA-stimulated monocytes and granulocytes (not on unstimulated cells), and inhibits binding of fibrinogen, factor X, and iC3b to Mac-1 as well as adhesion to immobilized ICAM-1. Flow cytometry binding assay, ligand inhibition assays, adhesion assays, clinical correlation Circulation High 10510057
1999 Mac-1 (CD11b/CD18) deficiency in mice reduces infarction volume by 26% and diminishes neutrophil infiltration after transient focal cerebral ischemia/reperfusion, demonstrating Mac-1-dependent neutrophil recruitment in brain ischemia-reperfusion injury. Mac-1-deficient mouse model, TTC staining for infarct volume, neutrophil histochemistry, laser-Doppler flowmetry Stroke High 9880401
1999 Beta2-integrin CD11b/CD18 activation involves an oxidative S-thiolation step in a tyrosine kinase-dependent signaling pathway; H2O2 directly induces CD11b/CD18-dependent adhesion and neoepitope expression, while diphenylene iodonium (flavoprotein oxidoreductase inhibitor) and free radical scavengers block agonist-induced beta2-integrin activation. Flow cytometry, adhesion assays, pharmacological inhibition, neutrophils from CGD patients European journal of immunology Medium 10556796
2000 Platelet GPIbα is a counter-receptor for leukocyte Mac-1 (CD11b/CD18); the interaction involves the Mac-1 I domain and the GPIbα leucine-rich repeat and C-terminal flanking regions; Mac-1-deficient mouse neutrophils fail to bind GPIbα and adherent platelets, and mocarhagin (GPIbα-cleaving protease) inhibits neutrophil-platelet adhesion. Adhesion assays with transfected cells, mAb inhibition, Mac-1-deficient mouse neutrophils, mocarhagin cleavage, flow-based adhesion assay The Journal of experimental medicine High 10899906
2000 Mac-1 (CD11b/CD18) forms membrane complexes with GPI-anchored uPAR (CD87), providing a transmembrane signaling mechanism; the lectin domain of CD11b forms a complex with uPAR, generating high-affinity adhesion, and this is reversed when uPA captures uPAR, causing it to bind a second CD11b site (residues 424-440). Receptor complex studies, functional adhesion assays, domain mapping Critical reviews in immunology Medium 10968371
2002 IL-8 activates Mac-1 (CD11b/CD18)-dependent neutrophil adhesion to fibrinogen via PI3K (upstream) and parallel MAPK and PKC pathways; PI3K inhibition blocks MAPK but not PKC activation, indicating a branch point before PI3K, while combined MAPK+PKC inhibition completely abolishes IL-8-stimulated adhesion. Pharmacological pathway inhibition, kinase activity assays, adhesion to purified fibrinogen Journal of immunology High 11971003
2002 CR3 (CD11b/CD18) and CR4 (CD11c/CD18) mediate complement-independent phagocytosis of IgM- and IgA-opsonized Cryptococcus neoformans; soluble GXM (which binds CD18) inhibits IgM/IgA-mediated but not IgG1-mediated phagocytosis; CHO cells expressing CR3 or CR4 demonstrate sufficient phagocytic function. mAb inhibition, CD18-deficient macrophages, CHO cell transfection, phagocytosis assays Immunity High 12121661
2002 Mac-1 (CD11b/CD18) functions as an accessory molecule for FcαRI (CD89)-mediated binding of secretory IgA (SIgA); Mac-1-deficient PMN fail to bind SIgA despite expressing FcαRI, and the secretory component alone binds Mac-1-expressing but not Mac-1-deficient PMN. Mac-1-deficient mouse PMN transgenic for human FcαRI, binding assays, respiratory burst assay Journal of immunology High 12244179
2002 The lectin domain of CD11b (near CBRM1/23 epitope, residues 943-1047) mediates high-affinity adhesion by forming a complex with uPAR; beta-glucan and uPAR compete for this site, linking Mac-1's adhesion and cytotoxic degranulation functions through a common lectin domain. Competitive binding assays, domain mapping, uPAR interaction studies Immunologic research Medium 12018461
2002 JAM-1 (junctional adhesion molecule 1) is a ligand of LFA-1 (CD11a/CD18) involved in transendothelial migration; JAM-1 membrane-proximal Ig-like domain 2 supports LFA-1-mediated T cell and neutrophil arrest and transmigration under flow conditions; chemokines redistribute JAM-1 from tight junctions to trigger LFA-1-dependent arrest. LFA-1 transfectant adhesion assays, blocking mAbs, flow chamber assays, JAM-1 domain truncation studies Nature immunology High 11812992
2003 Cytoplasmic domain separation of the alphaL and beta2 (CD18) subunits underlies bidirectional LFA-1 signaling; FRET between CFP-alphaL and YFP-beta2 cytoplasmic tails in living cells showed these domains are close in resting state but separate upon intracellular activation (inside-out) or ligand binding (outside-in). FRET with CFP/YFP-tagged cytoplasmic domains in living cells, inside-out and outside-in activation conditions Science High 14500982
2003 The extracellular membrane-proximal regions of CD11b and CD18 subunits constrain the receptor in a low-adhesive state; perturbation of these regions in either subunit enhances adhesion via conformational change (not receptor clustering or lipid raft association), and the CD11b subunit plays a more important role in maintaining inactive state. Site-directed mutagenesis, ligand binding assays, receptor clustering analysis, lipid raft fractionation Journal of immunology High 12847278
2004 Multiple binding sites exist in fibrinogen for Mac-1 (alphaMbeta2): the alphaM I-domain binds multiple sites in the gammaC and betaC domains of fibrinogen. I-domain binding depends on basic and hydrophobic residues. The 'I-less' form of alphaMbeta2 does not support adhesion, confirming the I-domain as the fibrinogen-binding site. Surface plasmon resonance, peptide library screening, synthetic peptide inhibition, 'I-less' receptor mutant cell adhesion The Journal of biological chemistry High 15304494
2004 LFA-1 (CD11a/CD18) alone is sufficient to trigger NK cell cytotoxicity; ICAM-1 expressed on Drosophila insect cells (lacking other human ligands) induced lysis by NK cells, and engagement of LFA-1 by ICAM-1- or ICAM-2-coated beads alone polarized cytotoxic granules toward the contact site. Drosophila insect cell expression system, bead-based LFA-1 engagement, granule polarization microscopy, NK cell cytotoxicity assays Journal of immunology High 15356110
2004 Mac-1 (CD11b/CD18) and ICAM-1 are essential for arteriogenesis (collateral artery growth); ICAM-1-/- and Mac-1-/- mice showed significantly reduced collateral conductance after femoral artery ligation (36% and 42% vs. 59% in controls), while selectin-deficient mice showed no defect. KO mouse models, laser-Doppler flowmetry with fluorescent microspheres, anti-ICAM-1 antibody treatment Circulation research High 15059933
2004 Plasminogen (Glu-Pg) is an adhesive ligand for integrin alphaMbeta2 (Mac-1); the alphaM I-domain is the binding site; the 'I-less' form of alphaMbeta2 fails to support adhesion and the recombinant I-domain binds Glu-Pg directly. mAb inhibition, I-less mutant receptor, recombinant I-domain binding assay, U937 and neutrophil adhesion assays Blood High 15090462
2006 Mac-1 (CD11b/CD18) on neutrophils recognizes complement C3 deposited within vessel walls and triggers signaling through Src-family kinase Hck and Syk tyrosine kinase, leading to neutrophil elastase release causing hemorrhage, fibrin deposition, and thrombosis; mice deficient in C3, Mac-1, Hck, Syk, or elastase are all protected. Genetic KO mice (Mac-1-/-, Hck-/-, Syk-/-, elastase-/-), bone marrow transfer, in vitro elastase release assays Immunity High 16872848
2006 Lipoprotein(a) [Lp(a)] specifically interacts with Mac-1 (beta2-integrin) through its apo(a) moiety (containing plasminogen kringle 4-like repeats), promoting monocyte adhesion and transendothelial migration; this interaction activates NF-κB and induces prothrombotic tissue factor expression. Binding assays, adhesion and migration assays, NF-κB activation assays, tissue factor expression, competitive inhibition with kringle 4 FASEB journal High 16403785
2006 LFA-1 nanoclusters (100-150 nm diameter) on monocytes contain primed LFA-1 molecules expressing the L16 activation epitope; these proactive nanoclusters are dynamically recruited to cell-cell interfaces forming micrometer-sized macroclusters linked to talin, demonstrating that avidity regulation involves at least three spatial organization states. High-resolution fluorescence mapping (near-field optical microscopy), live cell imaging of monocyte-T cell conjugates, talin co-localization Molecular biology of the cell High 16855029
2006 Talin1 is required for TCR-mediated LFA-1 (CD11a/CD18) activation; siRNA depletion of talin1 impairs TCR-induced LFA-1 affinity upregulation, LFA-1 polarization, ICAM-1 adhesion, and T cell-APC conjugation; restoring LFA-1 affinity alone (without talin1) is insufficient to restore full adhesive function. siRNA knockdown in human T cells, ICAM-1 adhesion assays, activation reporter antibody binding, T cell-APC conjugation assay Journal of immunology High 17114441
2007 Rap1 GTPase is central to LFA-1 inside-out signaling; TCR/CD28 signals activate Rap1 through ADAP/SKAP-55 adaptor proteins, and Rap1-GTP acts through RAPL and RIAM to act on the CD18 cytoplasmic domain and increase LFA-1 ectodomain adhesion; outside-in LFA-1 signaling activates Vav-1 (RhoGEF) and downstream Ras through PLD-RasGRP1. Genetic and pharmacological perturbation studies, Rap1 activity assays, signaling cascade analysis in T cells Immunological reviews Medium 17624948
2008 Myeloperoxidase (MPO) delays neutrophil apoptosis by signaling through CD11b/CD18 independently of its catalytic activity; MPO binding to CD11b/CD18 activates ERK and Akt, leading to phosphorylation of Bad at Ser112 and Ser136, preventing mitochondrial dysfunction and caspase-3 activation. mAb inhibition, pharmacological inhibitors of ERK/Akt/caspase-3, Bad phosphorylation assay, apoptosis assays, in vivo carrageenan lung injury model Circulation research High 18617697
2008 MMP-9 (gelatinase B) sheds the CD18 (beta2 integrin subunit) ectodomain from macrophages; active MMP-9 cleaves a single peptide site corresponding to Ala705-Ile706 of CD18, identified by peptide library substrate mapping and MS detection of cleavage peptides only in MMP-9-overexpressing macrophages. Subtractive proteomics (2D-LC-MS/MS), overlapping peptide library cleavage assay, autoactivating MMP-9 macrophage model Molecular & cellular proteomics High 19116209
2009 Mac-1 (CD11b/CD18) outside-in signaling requires global conformational activation (switchblade-like extension and cytoplasmic tail separation) but not integrin clustering; FRET showed ligand occupancy or activating Ab binding—but not clustering alone—triggered extension and alphaM/beta2 tail separation, inducing Akt phosphorylation and inhibiting neutrophil apoptosis. FRET in human neutrophils and K562 cells, Akt phosphorylation assay, apoptosis assay, conformational reporter antibodies Journal of immunology High 19864611
2010 Calpain 2 controls turnover of LFA-1 (CD11a/CD18) adhesions during T lymphocyte migration; inhibition of calpain 2 (by siRNA or pharmacological inhibitors) prevents LFA-1 adhesion disassembly causing T cell elongation and shedding of LFA-1 clusters; calpain 2 is most active at the trailing edge and requires Ca2+ influx (not through ORAI1). siRNA silencing, pharmacological inhibition, live cell imaging, CMAC,t-BOC-Leu-Met fluorescent calpain substrate, ORAI1-mutant patient T cells PloS one High 21152086
2011 A subset of human neutrophils suppresses T cell proliferation through Mac-1 (CD11b/CD18)-dependent release of hydrogen peroxide into the immunological synapse; Mac-1 expression is required for this suppression, as Mac-1-deficient neutrophils cannot perform this function. Human neutrophil subset isolation, T cell proliferation assays, H2O2 measurement, Mac-1-deficient mouse neutrophils The Journal of clinical investigation High 22156198
2012 Neutrophil LFA-1 (CD11a/CD18) arrest is regulated by inside-out signaling through CXCR2; CXCR2 signaling induces LFA-1 conformational changes (extended with open I domain) for firm arrest, while PSGL-1 engagement induces a distinct extended-with-closed-I-domain state for slow rolling; talin-1 and Kindlin-3 are critical co-activators with distinct roles. Intravital microscopy, flow chambers, conformation-specific reporter antibody binding, talin-1 and Kindlin-3 functional studies Frontiers in immunology High 22701459
2013 CD11c (alphaX) chain phosphorylation at Ser-1158 is essential for CD11c/CD18 adhesion and phagocytosis; mutation of this site abolishes CD11c/CD18 function, paralleling the known importance of alpha-chain phosphorylation for CD11a/CD18 and CD11b/CD18 function. Phosphorylation site identification, site-directed mutagenesis, adhesion and phagocytosis assays The Journal of biological chemistry High 24129562
2015 Contact-activated C3 (C3(H2O)) on activated platelets acts as a novel ligand for CD11b/CD18, mediating platelet-PMN complex formation; direct binding of C3(H2O) to CD11b/CD18 was confirmed by quartz crystal microbalance with purified proteins, and CD11b/CD18 transfectants specifically adhere to surface-bound C3(H2O). Quartz crystal microbalance with purified proteins, flow cytometry, CD18-deficient patient blood, transfectant adhesion assays Thrombosis and haemostasis High 26293614
2016 Human cathelicidin peptide LL-37 is a ligand for Mac-1 (integrin alphaMbeta2/CD11b/CD18); LL-37 binds the alphaM I-domain and promotes phagocytosis of LL-37-coated bacteria by macrophages; Mac-1-deficient macrophages fail to show enhanced phagocytosis of LL-37-coated beads. HEK293 transfection with Mac-1, mAb inhibition, Mac-1-deficient macrophage phagocytosis assays, bead phagocytosis model Research and reports in biochemistry High 27990411
2017 SLAMF7 on macrophages and tumor cells interacts with Mac-1 integrin (CD11b/CD18) to mediate phagocytosis of haematopoietic tumor cells during SIRPα-CD47 blockade; this phagocytosis is independent of SAP adaptors but dependent on Mac-1 interaction and ITAM signaling. SLAM family KO mice, Mac-1 interaction studies, in vitro and in vivo phagocytosis assays, SAP-deficient cells Nature High 28424516
2017 Extracellular ISG15 signals IFN-γ secretion through LFA-1 (CD11a/CD18) as the cell surface receptor; ISG15 binds directly to the alphaL I domain of CD11a in vitro; LFA-1 inhibition or CD11a knockout blocks ISG15-induced cytokine secretion; ISG15 engagement of LFA-1 activates Src family kinases. NK-92 cell IFN-γ assay, CD11a-/- splenocytes, direct in vitro binding to alphaI domain, SFK inhibition studies Molecular cell High 29100055
2017 Leukocyte Mac-1 (CD11b/CD18) regulates thrombosis via interaction with platelet GPIbα; Mac-1-deficient mice and mice with mutation of the GPIbα-binding site on Mac-1 show delayed thrombosis after arterial injury; adoptive wild-type leukocyte transfer rescues the thrombosis defect; Mac-1 engagement regulates transcription factor Foxp1 to contribute to thrombosis. Mac-1-deficient KO and knock-in mice, adoptive transfer, carotid/cremaster microvascular injury models, Foxp1 conditional overexpression Nature communications High 28555620
2018 LC3-associated phagocytosis (LAP) of Listeria monocytogenes is initiated by integrin Mac-1 (ITGAM-ITGB2/CD11b/CD18); in tissue macrophages, Listeria are targeted exclusively by Mac-1-initiated LAP (not canonical autophagy), which is required for bacterial killing and anti-listerial immunity in vivo. In vivo mouse infection model, Mac-1-deficient mice, LAP vs. canonical autophagy genetic dissection Autophagy High 29923444
2018 LFA-1 (CD11a/CD18) mediates T cell migration and differentiation through inside-out signaling (regulated by Rap1, talin, Kindlin-3) and outside-in signaling; in T cells, LFA-1 adhesion to ICAM-1 facilitates firm endothelial adhesion, prolonged APC contact, and cytotoxic killing. Summary of multiple mechanistic studies (review with primary experimental basis) Frontiers in immunology Medium 29774029
2019 Mac-1 (CD11b/CD18) stimulation of neutrophils by opsonized microorganisms drives the formation of antibacterial extracellular vesicles (EVs) through tyrosine kinase signaling; Mac-1/CR3 activation (but not Fc receptors or PRRs alone) determines EV numbers, cargo, and antibacterial capacity; Mac-1/CR3 signaling is not required for spontaneous EV formation. Mac-1-deficient mice, flow cytometry, proteomics, functional antibacterial EV assay, tyrosine kinase inhibitors Journal of extracellular vesicles High 31853340
2019 LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) both bind ICAM-1 and reciprocally determine the direction of neutrophil migration on endothelium; when Mac-1 is blocked, both HL-60 cells and primary neutrophils migrate upstream (against flow) via LFA-1; unblocked, they migrate downstream, demonstrating opposing migratory directionality functions. Flow chamber assays on ICAM-1 surfaces and activated endothelium, mAb blocking of Mac-1 vs. LFA-1 Biophysical journal High 31585707
2020 ITGB2 (CD18) in cancer-associated fibroblasts (CAFs) activates the PI3K/AKT/mTOR pathway to enhance glycolysis, causing lactate release that is absorbed by OSCC cells for NADH oxidation in mitochondrial OXPHOS to produce ATP, promoting tumor proliferation; MCT1 knockdown or metformin treatment blocks this pathway. Co-culture assays, siRNA knockdown of MCT1, in vitro/in vivo proliferation assays, GC/MS metabolomics, western blot Theranostics Medium 33204328
2020 Tensile force transmitted through LFA-1 (CD11a/CD18) bonds on neutrophils drives mechanotransduction via assembly of a Kindlin-3/RACK1/Orai1 cytosolic complex; force on LFA-1 causes RACK1 dissociation forming a gradient above LFA-1 clusters, directing ER translocation proximal to Orai1 for IP3R1/STIM1-mediated Ca2+ influx and neutrophil shape change and migration. Live cell imaging, Ca2+ flux assays, shear stress manipulation, Kindlin-3/RACK1 interaction studies, Orai1 channel measurements Journal of leukocyte biology High 32531836
2023 ITGAM and ITGB2 expressed on extracellular vesicles from severe acute pancreatitis mediate pulmonary accumulation of pancreas-derived EVs and promote acute lung injury; EVs engineered to overexpress ITGAM and ITGB2 compete with endogenous SAP-EVs for pulmonary accumulation, attenuating inflammation. Integrin antagonist peptide (HYD-1) pretreatment, engineered EV overexpression in SAP mice, pulmonary inflammation and endothelial barrier assays ACS nano Medium 37022097

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). Journal of immunology (Baltimore, Md. : 1950) 2478 3086451
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Integrins. Cell and tissue research 1256 19693543
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1998 Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proceedings of the National Academy of Sciences of the United States of America 922 9736715
1990 ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). The Journal of cell biology 898 1980124
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 The DNA sequence of human chromosome 21. Nature 808 10830953
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
1998 A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 749 9419363
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. The Journal of clinical investigation 680 22156198
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1988 ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature 642 3340213
2003 Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science (New York, N.Y.) 618 14500982
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
1987 Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell 508 3028646
1999 Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 507 10548107
2002 JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nature immunology 499 11812992
1991 Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1. The Journal of experimental medicine 499 1676048
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
1993 The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands. The Journal of cell biology 479 7679388
1988 A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits. The Journal of clinical investigation 479 3278007
2000 Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). The Journal of experimental medicine 471 10899906
2010 Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. Journal of immunology (Baltimore, Md. : 1950) 461 20511548
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2012 HIV: cell binding and entry. Cold Spring Harbor perspectives in medicine 416 22908191
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1996 Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule. Cell 386 8706128
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
1987 Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency. Cell 349 3594570
1988 Oligospecificity of the cellular adhesion receptor Mac-1 encompasses an inducible recognition specificity for fibrinogen. The Journal of cell biology 343 3053736
2003 Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling. Proceedings of the National Academy of Sciences of the United States of America 341 12606711
1991 Characterization of the rat leukocyte integrin, CD11/CD18, by the use of LFA-1 subunit-specific monoclonal antibodies. European journal of immunology 268 1672643
1995 CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. The Journal of experimental medicine 247 7535339
2004 LFA-1 contributes an early signal for NK cell cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 240 15356110
2017 SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature 238 28424516
1995 Ins and outs of LFA-1. Immunology today 232 7576051
1989 Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding to different ligands. Journal of immunology (Baltimore, Md. : 1950) 222 2809204
1991 CD40 signaling activates CD11a/CD18 (LFA-1)-mediated adhesion in B cells. Journal of immunology (Baltimore, Md. : 1950) 218 1706378
1995 L-selectin (CD62L) cross-linking signals neutrophil adhesive functions via the Mac-1 (CD11b/CD18) beta 2-integrin. Journal of immunology (Baltimore, Md. : 1950) 209 7543524
2018 LFA-1 in T Cell Migration and Differentiation. Frontiers in immunology 204 29774029
1993 Gene targeting yields a CD18-mutant mouse for study of inflammation. Journal of immunology (Baltimore, Md. : 1950) 191 8101543
1999 Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 188 9880401
2017 Extracellular ISG15 Signals Cytokine Secretion through the LFA-1 Integrin Receptor. Molecular cell 186 29100055
1995 Leukocyte CD11/CD18 integrins: biological and clinical relevance. Haematologica 180 7628754
2000 Regulation of the adhesion versus cytotoxic functions of the Mac-1/CR3/alphaMbeta2-integrin glycoprotein. Critical reviews in immunology 173 10968371
1990 A unique recognition site mediates the interaction of fibrinogen with the leukocyte integrin Mac-1 (CD11b/CD18). The Journal of biological chemistry 166 1973686
2008 Myeloperoxidase delays neutrophil apoptosis through CD11b/CD18 integrins and prolongs inflammation. Circulation research 158 18617697
2012 The leucocyte β2 (CD18) integrins: the structure, functional regulation and signalling properties. Bioscience reports 144 22458844
2004 Arteriogenesis proceeds via ICAM-1/Mac-1- mediated mechanisms. Circulation research 138 15059933
2017 Leukocyte integrin Mac-1 regulates thrombosis via interaction with platelet GPIbα. Nature communications 137 28555620
2002 CR3 (CD11b/CD18) and CR4 (CD11c/CD18) are involved in complement-independent antibody-mediated phagocytosis of Cryptococcus neoformans. Immunity 136 12121661
1995 Activation of human neutrophils through L-selectin and Mac-1 molecules. Journal of immunology (Baltimore, Md. : 1950) 135 7532664
1989 An immobile subset of plasma membrane CD11b/CD18 (Mac-1) is involved in phagocytosis of targets recognized by multiple receptors. Journal of immunology (Baltimore, Md. : 1950) 132 2538507
1991 Occupancy of CD11b/CD18 (Mac-1) divalent ion binding site(s) induces leukocyte adhesion. Journal of immunology (Baltimore, Md. : 1950) 130 1890307
1989 Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation. Blood 122 2562920
1990 Impaired transendothelial migration by neonatal neutrophils: abnormalities of Mac-1 (CD11b/CD18)-dependent adherence reactions. Blood 120 1979926
2020 ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system. Theranostics 118 33204328
2017 Role of LFA-1 and ICAM-1 in Cancer. Cancers 113 29099772
2006 Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 113 16403785
2012 Neutrophil arrest by LFA-1 activation. Frontiers in immunology 110 22701459
2016 The many faces of Mac-1 in autoimmune disease. Immunological reviews 107 26683153
2006 Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Immunity 103 16872848
2004 Multiple binding sites in fibrinogen for integrin alphaMbeta2 (Mac-1). The Journal of biological chemistry 96 15304494
2006 Organization of the integrin LFA-1 in nanoclusters regulates its activity. Molecular biology of the cell 94 16855029
1999 Heparin inhibits ligand binding to the leukocyte integrin Mac-1 (CD11b/CD18). Circulation 94 10510057
1990 Point mutations impairing cell surface expression of the common beta subunit (CD18) in a patient with leukocyte adhesion molecule (Leu-CAM) deficiency. The Journal of clinical investigation 90 1968911
2006 Talin1 regulates TCR-mediated LFA-1 function. Journal of immunology (Baltimore, Md. : 1950) 88 17114441
1998 Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice. The American journal of physiology 84 9843832
1998 Interaction of the fungal pathogen Candida albicans with integrin CD11b/CD18: recognition by the I domain is modulated by the lectin-like domain and the CD18 subunit. Journal of immunology (Baltimore, Md. : 1950) 83 9834106
2008 MMP-9 sheds the beta2 integrin subunit (CD18) from macrophages. Molecular & cellular proteomics : MCP 79 19116209
2007 Small GTPases and LFA-1 reciprocally modulate adhesion and signaling. Immunological reviews 75 17624948
2002 Role of the lectin domain of Mac-1/CR3 (CD11b/CD18) in regulating intercellular adhesion. Immunologic research 75 12018461
1998 CD11/CD18 and CD14 share a common lipid A signaling pathway. Journal of immunology (Baltimore, Md. : 1950) 75 9820516
1996 Adaptation to eccentric exercise: effect on CD64 and CD11b/CD18 expression. Journal of applied physiology (Bethesda, Md. : 1985) 75 8847330
1992 Identification and sequence analysis of the promoter for the leukocyte integrin beta-subunit (CD18): a retinoic acid-inducible gene. Blood 75 1346252
2002 Signaling pathways involved in IL-8-dependent activation of adhesion through Mac-1. Journal of immunology (Baltimore, Md. : 1950) 73 11971003
2002 The GP IIb/IIIa inhibitor abciximab (c7E3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, alphaMbeta2). Thrombosis research 71 12431477
1999 A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics 68 10512685
2016 CD11c/CD18 Dominates Adhesion of Human Monocytes, Macrophages and Dendritic Cells over CD11b/CD18. PloS one 67 27658051
1988 Quantitation of intracellular Mac-1 (CD11b/CD18) pools in human neutrophils. Journal of leukocyte biology 67 2903896
2018 LncRNA ITGB2-AS1 Could Promote the Migration and Invasion of Breast Cancer Cells through Up-Regulating ITGB2. International journal of molecular sciences 66 29941860
2005 Manifestations of inflammatory arthritis are critically dependent on LFA-1. Journal of immunology (Baltimore, Md. : 1950) 66 15749905
1992 Cloning and analysis of the CD18 promoter. Blood 62 1350225
1990 Correction of CD18-deficient lymphocytes by retrovirus-mediated gene transfer. Science (New York, N.Y.) 62 1972597
1988 Modulation of surface CD11/CD18 glycoproteins (Mo1, LFA-1, p150,95) by human mononuclear phagocytes. Clinical immunology and immunopathology 62 3123109
2005 Spermine, a natural polyamine, suppresses LFA-1 expression on human lymphocyte. Journal of immunology (Baltimore, Md. : 1950) 61 15972654
1993 Regulation of CD11b/CD18 expression in human neutrophils by phospholipase A2. Journal of immunology (Baltimore, Md. : 1950) 57 8228253
1992 Mobilization of an intracellular glycoprotein (Mac-1) on monocytes and granulocytes during hemodialysis. American journal of nephrology 57 1292337
2009 Outside-in signal transmission by conformational changes in integrin Mac-1. Journal of immunology (Baltimore, Md. : 1950) 56 19864611
2004 How T cells use LFA-1 to attach and migrate. Immunology letters 56 15081527
2007 Human CD18 is the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin. Infection and immunity 54 17635865
2002 Mac-1 (CD11b/CD18) as accessory molecule for Fc alpha R (CD89) binding of IgA. Journal of immunology (Baltimore, Md. : 1950) 52 12244179
1999 Redox regulation of beta2-integrin CD11b/CD18 activation. European journal of immunology 50 10556796
2016 Identification of Human Cathelicidin Peptide LL-37 as a Ligand for Macrophage Integrin αMβ2 (Mac-1, CD11b/CD18) that Promotes Phagocytosis by Opsonizing Bacteria. Research and reports in biochemistry 48 27990411
1997 Ropivacaine inhibits leukocyte rolling, adhesion and CD11b/CD18 expression. The Journal of pharmacology and experimental therapeutics 46 9336308
1995 A peptide derived from the intercellular adhesion molecule-2 regulates the avidity of the leukocyte integrins CD11b/CD18 and CD11c/CD18. The Journal of cell biology 46 7744962
1993 Upregulation of Mac-1 surface expression on neutrophils during simulated extracorporeal circulation. The Journal of laboratory and clinical medicine 46 8426073
2010 Calpain 2 controls turnover of LFA-1 adhesions on migrating T lymphocytes. PloS one 45 21152086
1999 How LFA-1 binds to different ligands. Immunology today 45 10322304
2000 Upregulation of CD14 and CD18 on monocytes In vitro by antineutrophil cytoplasmic autoantibodies. Journal of the American Society of Nephrology : JASN 44 10966488
2013 Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils. Arthritis and rheumatism 43 23918739
2007 Binding between the integrin alphaXbeta2 (CD11c/CD18) and heparin. The Journal of biological chemistry 42 17699512
2018 Neutrophil-mediated Suppression of Influenza-induced Pathology Requires CD11b/CD18 (MAC-1). American journal of respiratory cell and molecular biology 41 29141155
2005 Neutrophil differentiated HL-60 cells model Mac-1 (CD11b/CD18)-independent neutrophil transepithelial migration. Immunology 41 15819703
2004 Characterization of plasminogen as an adhesive ligand for integrins alphaMbeta2 (Mac-1) and alpha5beta1 (VLA-5). Blood 41 15090462
1996 Lymphocytes utilize CD11b/CD18 for adhesion to Candida albicans. Cellular immunology 41 8660804
1990 Contribution of CR3, CD11b/CD18 to cytolysis by human NK cells. Molecular immunology 40 1980339
2023 Extracellular Vesicle ITGAM and ITGB2 Mediate Severe Acute Pancreatitis-Related Acute Lung Injury. ACS nano 38 37022097
1998 ICAM-1-CD18 interaction mediates neutrophil cytotoxicity through protease release. The American journal of physiology 38 9611129
2004 Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion. Blood 37 15073035
2015 Contact activation of C3 enables tethering between activated platelets and polymorphonuclear leukocytes via CD11b/CD18. Thrombosis and haemostasis 36 26293614
1994 Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation. Blood 36 7514906
2019 Human Neutrophils Will Crawl Upstream on ICAM-1 If Mac-1 Is Blocked. Biophysical journal 35 31585707
2002 Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 co-dependent. Gut 35 11950807
1986 Expression of the leukocyte functional molecule (LFA-1) on mouse platelets. Blood 33 3518835
1996 Passage of CD18- and CD18+ bovine neutrophils into pulmonary alveoli during acute Pasteurella haemolytica pneumonia. Veterinary pathology 30 8952022
2001 Novel SNPs in the CD18 gene validate the association with MPO-ANCA+ vasculitis. Genes and immunity 29 11528520
2013 Integrin CD11c/CD18 α-chain phosphorylation is functionally important. The Journal of biological chemistry 28 24129562
2000 The accumulation of dendritic cells in the lung is impaired in CD18-/- but not in ICAM-1-/- mutant mice. Journal of immunology (Baltimore, Md. : 1950) 28 10679084
2023 Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model. Frontiers in immunology 27 37063847
2006 Distinct roles of Mac-1 and its counter-receptors in neonatal obstructive nephropathy. Kidney international 27 16374427
2019 Role of Mac-1 integrin in generation of extracellular vesicles with antibacterial capacity from neutrophilic granulocytes. Journal of extracellular vesicles 26 31853340
2003 Modulation of CD11b/CD18 adhesive activity by its extracellular, membrane-proximal regions. Journal of immunology (Baltimore, Md. : 1950) 25 12847278
1993 Monoclonal antibodies to the carbohydrate structure Lewis(x) stimulate the adhesive activity of leukocyte integrin CD11b/CD18 (CR3, Mac-1, alpha m beta 2) on human granulocytes. Journal of leukocyte biology 25 8099115
2022 The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer. Journal of clinical medicine 24 36362654
2018 LC3-associated phagocytosis initiated by integrin ITGAM-ITGB2/Mac-1 enhances immunity to Listeria monocytogenes. Autophagy 24 29923444
2020 Tensile force transmitted through LFA-1 bonds mechanoregulate neutrophil inflammatory response. Journal of leukocyte biology 21 32531836