Affinage

ITGAM

Integrin alpha-M · UniProt P11215

Length
1152 aa
Mass
127.2 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGAM (CD11b) is the α-chain of the β2-integrin Mac-1/CR3 (CD11b/CD18), a myeloid multi-ligand adhesion and signaling receptor that couples leukocyte recognition of opsonized and microbial surfaces to phagocytosis, migration, and the tuning of inflammatory output (PMID:8485905, PMID:2153038). As a promiscuous receptor it engages iC3b, ICAM-1, β-glucan, fibrinogen, oligodeoxynucleotides, the platelet receptor GPIbα, and bacterial adhesins, with ligand engagement driving phagocytosis and adhesion-dependent reactive oxygen production while constraining β2-dependent migration (PMID:8485905, PMID:9095175, PMID:19752320, PMID:16239529). Its activation state is switched on by oxidative S-thiolation downstream of tyrosine kinase signaling and by NO–guanylate cyclase–cGMP–PKG–CREB signaling that upregulates surface CD11b (PMID:10556796, PMID:16551637). Beyond adhesion, activated CD11b acts as a negative regulator of inflammation: it suppresses TLR-dependent inflammatory and type I interferon responses through an AKT/FOXO3/IRF3/IRF7 axis (PMID:28263189), dampens BCR signaling by directly binding CD22 to recruit SHP-1 and enforce autoreactive B cell tolerance (PMID:24264377), and restrains Mincle/Syk-driven macrophage inflammation by assembling a Lyn–SIRPα–SHP1 complex that dephosphorylates Syk (PMID:29400702). Through these activities CD11b governs macrophage polarization (via Let-7a/cMyc) (PMID:30568188), the dendritic-cell IL-6–driven Treg/Th17 balance (PMID:28191643), and tissue inflammation in hypertensive vascular and cardiac remodeling (PMID:36377602, PMID:36822392). Lupus-associated loss-of-function variants, notably R77H/rs1143679, impair phagocytosis, adhesion, and TLR/IFN-I suppression, mechanistically linking reduced CD11b activity to SLE pathogenesis (PMID:22586164, PMID:28263189), and small-molecule agonists (LA1, ADH-503) restore these regulatory functions in disease models (PMID:28263189, PMID:31270275). The ITGAM promoter is directly activated by the GABP transcription factor through a myeloid-specific minimal element, and expression rises coordinately with myeloid differentiation at the mRNA level (PMID:1683702, PMID:2562920, PMID:26170143).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1990 High

    Established the storage and mobilization logic of CD11b, showing it is held in neutrophil secondary granules and rapidly delivered to the surface on activation — explaining how CD11b function is regulated by translocation rather than synthesis.

    Evidence Subcellular fractionation and surface expression measurement before/after FMLP stimulation in neonatal vs adult neutrophils

    PMID:2153038

    Open questions at the time
    • Did not define the trafficking machinery linking granule release to activation
    • Mechanism of the neonatal translocation defect not resolved
  2. 1991 Medium

    Localized myeloid-specific, developmentally regulated CD11b expression to a minimal 242 bp promoter, establishing transcriptional control of the gene during myelopoiesis.

    Evidence Promoter cloning, transcription start site mapping, and promoter-reporter assays in cell lines

    PMID:1683702

    Open questions at the time
    • Did not identify the specific transcription factors binding the element
    • Endogenous chromatin context not tested
  3. 1993 Medium

    Defined CR3 as a multi-ligand adhesion and phagocytic/cytotoxicity receptor whose β-glucan engagement primes recognition of iC3b-coated targets, framing CD11b as a dual adhesion/effector receptor.

    Evidence Functional binding, phagocytosis and cytotoxicity assays with β-glucan and anti-CR3 antibodies

    PMID:8485905

    Open questions at the time
    • Ligand-binding sites within CD11b not mapped
    • Signaling downstream of activated receptor not defined
  4. 1997 High

    Showed Mac-1 binds oligodeoxynucleotides at sites overlapping its fibrinogen ligand and couples this to functional outputs (inhibited migration, increased ROS), revealing that ligand occupancy redirects neutrophil behavior.

    Evidence Competitive binding, antibody blocking, Matrigel migration and ROS assays in PMNs

    PMID:9095175

    Open questions at the time
    • Physiological relevance of ODN binding unclear
    • Structural basis of shared binding site not defined
  5. 1999 High

    Identified an oxidative S-thiolation mechanism downstream of tyrosine kinase signaling as the switch driving CD11b/CD18 activation, connecting redox state to integrin conformational activation.

    Evidence Neutrophil adhesion and activation-neoepitope (mAb 24) assays with kinase, sulfhydryl, and oxidase inhibitors

    PMID:10556796

    Open questions at the time
    • Specific cysteine residues modified not identified
    • Link between thiolation and conformational change not structurally resolved
  6. 2005 High

    Demonstrated CR3 serves as the receptor for the Bordetella adhesin FHA and that ligand binding, not surface expression level, governs phagocytic signaling — separating receptor abundance from functional activation.

    Evidence Anti-CR3 blocking, bacterial mutant panel, and dissociation of expression from phagocytosis

    PMID:16239529

    Open questions at the time
    • Signaling events triggering phagocytosis not dissected
    • How some toxins evade CR3-mediated uptake unresolved
  7. 2006 High

    Established a NO–guanylate cyclase–cGMP–PKG–CREB pathway as a transcriptional route to CD11b upregulation in microglia, identifying a second activation input distinct from redox/conformational switching.

    Evidence Pharmacological node-by-node dissection with NO donors/scavengers and GC/PKG inhibitors in microglia, plus in vivo microinjection

    PMID:16551637

    Open questions at the time
    • CREB target sites in the ITGAM promoter not mapped
    • Generalizability beyond microglia not tested
  8. 2009 High

    Placed Mac-1 at the inflammation–thrombosis interface by showing its interaction with platelet GPIbα drives glomerular thrombosis, defining a specific molecular bridge between neutrophils and platelets.

    Evidence Mac-1-deficient mice, cell depletions, and antibody blockade of the Mac-1–GPIbα interaction in glomerulonephritis

    PMID:19752320

    Open questions at the time
    • Structural basis of Mac-1–GPIbα binding not defined
    • Contribution relative to other Mac-1 ligands in thrombosis unclear
  9. 2012 High

    Provided the first mechanistic link between the lupus risk allele R77H/rs1143679 and CR3 dysfunction, showing the variant impairs phagocytosis, adhesion, and TLR suppression without altering expression.

    Evidence Functional assays in primary human monocytes from genotyped donors plus variant-specific transfection in COS7 cells

    PMID:22586164

    Open questions at the time
    • Structural consequence of R77H on the receptor not resolved
    • Which downstream pathway loss dominates SLE risk not isolated
  10. 2013 High

    Revealed a non-adhesive, intracellular-signaling role: CD11b directly binds CD22 to recruit SHP-1 and restrain BCR signaling, with R77H abrogating this — explaining how loss of CD11b activity breaks autoreactive B cell tolerance.

    Evidence Co-IP of CD22-CD11b, BCR proliferation/phospho/calcium assays in CD11b-deficient B cells, variant rescue, and in vivo engagement

    PMID:24264377

    Open questions at the time
    • Stoichiometry and structural interface of CD11b-CD22 binding not defined
    • How CD11b ligand engagement couples to CD22 recruitment unclear
  11. 2017 High

    Defined CD11b as a brake on TLR-driven inflammation and type I interferon via an AKT/FOXO3/IRF3/IRF7 axis, and showed pharmacological activation (LA1) reverses elevated IFN-I in lupus models and human SNP-carrier cells.

    Evidence LA1 agonist, CD11b-deficient and MRL/Lpr mice, pathway analysis, and macrophages from human ITGAM SNP carriers

    PMID:28263189

    Open questions at the time
    • How integrin signaling engages AKT/FOXO3 mechanistically not fully resolved
    • Cell-type-specific contributions not delineated
  12. 2017 High

    Placed CD11b upstream of the IL-6/Th17 axis, showing CD11b-deficient dendritic cells overproduce IL-6 to skew the Treg/Th17 balance and worsen arthritis, rescuable by CD11b+ DC transfer or IL-6R blockade.

    Evidence CD11b-KO CIA arthritis model, DC–T cell co-culture, anti-IL-6R blockade, and adoptive transfer rescue

    PMID:28191643

    Open questions at the time
    • Mechanism by which CD11b restrains DC IL-6 production not defined
    • Direct vs indirect effects on Treg not separated
  13. 2018 High

    Identified the molecular machinery of CD11b's inflammatory brake in macrophages — a Mincle-CD11b complex recruiting Lyn-SIRPα-SHP1 to dephosphorylate Syk — generalizing the negative-regulatory function to anti-microbial signaling.

    Evidence Co-IP of the Mincle-CD11b complex, CD11b-KO macrophages, Syk phospho assays, and Lyn activator in a mycobacterial model

    PMID:29400702

    Open questions at the time
    • Order of assembly of the Lyn-SIRPα-SHP1 complex not resolved
    • Whether this complex operates outside Mincle signaling untested
  14. 2018 High

    Connected CD11b activation state to macrophage polarization through a Let-7a/cMyc switch, showing CD11b controls myeloid phenotype rather than recruitment and that agonism (LA1) suppresses tumor growth.

    Evidence CD11b KO and LA1 activation, Let-7a/cMyc expression analysis, and multiple tumor models

    PMID:30568188

    Open questions at the time
    • How integrin signaling regulates Let-7a transcription unknown
    • Link between polarization switch and the AKT/FOXO3 pathway not integrated
  15. 2019 Medium

    Translated CD11b agonism to cancer immunotherapy, showing ADH-503 repolarizes tumor-associated macrophages and sensitizes resistant tumors to checkpoint blockade.

    Evidence ADH-503 agonist in murine PDAC models with flow cytometry and checkpoint inhibitor combination

    PMID:31270275

    Open questions at the time
    • Molecular mechanism of repolarization not dissected
    • Off-target and dose-dependent effects of partial activation not defined
  16. 2019 High

    Defined the structural basis of CD11b's role as a toxin receptor, showing the staphylococcal leukocidin LukGH binds the CD11b α-I domain and that human CD11b drives the oligomerization required for cytolysis.

    Evidence Crystal structures of LukGH with human/murine CD11b-I, SAXS, engineered variants, and cytolysis assays

    PMID:31852826

    Open questions at the time
    • Physiological consequence of LukGH-CD11b interaction in infection not quantified
    • Whether endogenous ligands use the same α-I interface unresolved
  17. 2020 High

    Extended CD11b's inflammatory role to cardiovascular disease, establishing that myeloid CD11b mediates macrophage adhesion/migration driving hypertension and vascular remodeling, with bidirectional pharmacological control.

    Evidence CD11b KO, bone marrow chimeras, neutralizing antibody and LA1 in Ang II/DOCA-salt hypertension models

    PMID:36377602

    Open questions at the time
    • Endothelial ligand engaged during recruitment not identified
    • Reconciliation with anti-inflammatory roles of CD11b in other contexts unaddressed
  18. 2020 High

    Identified a chondroprotective function in which CD11b signaling suppresses IL-6-driven chondrocyte hypertrophy and mineralization, with deficiency worsening osteoarthritis.

    Evidence CD11b-KO chondrocytes, mineralization/Alp assays, anti-IL-6R blockade, LA1 agonist, and an in vivo meniscectomy OA model

    PMID:33392201

    Open questions at the time
    • How CD11b is engaged on chondrocytes mechanistically unclear
    • Source of relevant CD11b ligand in cartilage not identified
  19. 2021 Medium

    Linked CD11b to mechanotransduction, showing reciprocal regulation with Piezo1 in stretch-responding macrophages and an actin-dependent role in mechanically driven inflammation.

    Evidence Static/cyclic stretch with reciprocal siRNA knockdown of CD11b and Piezo1 and actin polymerization inhibition

    PMID:34630381

    Open questions at the time
    • Direct physical interaction with Piezo1 not demonstrated
    • Molecular basis of reciprocal expression regulation unknown
  20. 2023 High

    Extended hypertensive disease mechanism to the heart, showing CD11b drives macrophage infiltration and M1 polarization in cardiac remodeling, with consistent bidirectional pharmacological modulation.

    Evidence CD11b KO, bone marrow chimeras, antibody and LA1 in Ang II/DOCA-salt cardiac models, plus macrophage-cardiomyocyte co-cultures

    PMID:36822392

    Open questions at the time
    • Paracrine mediators of cardiomyocyte enlargement not fully defined
    • Why agonism worsens cardiac/vascular disease but protects in lupus/arthritis not mechanistically reconciled
  21. 2023 High

    Expanded the CD11b interactome by identifying Siglec-15 as a sialoglycan-dependent binding partner on human T cells, suggesting a role in T-cell-directed immune regulation.

    Evidence Siglec-15 crystal structure, STD-NMR, molecular dynamics, and binding-partner identification on T cells

    PMID:37311743

    Open questions at the time
    • Functional consequence of Siglec-15-CD11b binding not established
    • Whether interaction occurs in cis or trans not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the same receptor produces opposing disease outcomes — anti-inflammatory/protective in lupus, arthritis, and osteoarthritis but pathogenic in hypertensive cardiovascular remodeling — and what governs the choice between its adhesion/phagocytic and intracellular negative-regulatory programs.
  • No unifying model linking ligand identity to signaling outcome
  • Structural consequences of R77H and of agonist binding not resolved at atomic level
  • Cell-type-specific signaling logic not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0038024 cargo receptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-1643685 Disease 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3
Partners
CD22CLEC4EFOLR2GP1BAITGB2LYNSIGLEC15SIRPA
Complex memberships
Mac-1/CR3 (CD11b/CD18)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 CR3 (CD11b/CD18) functions both as an adhesion molecule and a phagocytic/cytotoxicity receptor with multiple ligand specificities, including iC3b, ICAM-1, bacterial carbohydrates/LPS, and soluble beta-glucan from yeast. Beta-glucan binding to CR3 induces an activated receptor state that permits neutrophil phagocytosis of iC3b-coated targets and NK cell cytotoxicity of iC3b-coated tumor cells that are normally resistant. Functional receptor binding assays, phagocytosis and cytotoxicity assays with beta-glucan and anti-CR3 antibodies Clinical and experimental immunology Medium 8485905
1997 Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein; binding occurs on both the αM (CD11b) and β2 (CD18) subunits. Soluble fibrinogen (a natural Mac-1 ligand) competes with oligodeoxynucleotide binding. Upregulation of Mac-1 surface expression increases oligodeoxynucleotide binding and internalization by PMNs. Mac-1-bound oligodeoxynucleotides inhibit β2-dependent migration through Matrigel while dramatically increasing reactive oxygen species production in PMNs adherent to fibrinogen. Competitive binding assays with fibrinogen, anti-Mac-1 monoclonal antibody blocking, surface expression upregulation, Matrigel migration assay, ROS production assay Nature medicine High 9095175
1990 Mac-1 (CD11b/CD18) is stored in gelatinase-rich (pre-gamma, secondary) granules of neutrophils and translocates to the plasma membrane upon chemotactic stimulation with FMLP. Neonatal neutrophils show diminished translocation of Mac-1 from these granular pools and reduced surface expression after FMLP stimulation, correlated with significantly lower gelatinase content, contributing to abnormal migratory properties. Subcellular fractionation, immunochemical assays, enzymatic gelatinase assays, surface expression measurement before and after FMLP stimulation comparing neonatal vs. adult neutrophils Blood High 2153038
1991 The CD11b gene promoter region extending 242 bp upstream and 71 bp downstream of the transcription initiation site is sufficient to direct myeloid-specific and developmentally regulated expression in vitro, mimicking endogenous CD11b expression. A single transcription initiation site was identified, and the minimal promoter contains binding sites for transcription factors involved in hematopoietic-specific and phorbol ester-inducible gene expression. Promoter cloning, transcription start site mapping, promoter-reporter assays in cell lines Proceedings of the National Academy of Sciences of the United States of America Medium 1683702
1989 CD11b/CD18 (Mo1) mRNA expression increases coordinately with cell surface protein expression during myeloid differentiation along both monocytic and granulocytic pathways in HL-60 cells, indicating regulation occurs at the mRNA level. Myeloid differentiation of HL-60 cells, mRNA quantification correlated with cell surface expression by flow cytometry Blood Medium 2562920
1999 CD11b/CD18 activation in neutrophils is regulated by an oxidative S-thiolation mechanism downstream of tyrosine kinase signaling. Exogenously added H2O2 induces CD11b/CD18-dependent adhesion and expression of an integrin activation neoepitope (mAb clone 24). This activation is inhibited by tyrosine kinase inhibitors and by complexing sulfhydryl groups with PAO. TNF-alpha-triggered CD11b/CD18 activation is blocked by the flavoprotein oxidoreductase inhibitor DPI and free radical scavengers. Neutrophil adhesion assays, integrin activation neoepitope detection (mAb 24), pharmacological inhibitors of tyrosine kinases, sulfhydryl reagents, oxidase inhibitors, and comparison with integrin-activating antibody (KIM 185) European journal of immunology High 10556796
2006 Nitric oxide (NO) upregulates CD11b expression in microglial cells via the guanylate cyclase (GC)-cGMP-PKG-CREB signaling pathway. LPS-induced NO production increases CD11b expression; this is blocked by NO scavengers (PTIO) or iNOS inhibitors (L-NIL). The NO donor GSNO directly induces CD11b expression, and inhibitors of GC (NS2028) or PKG (KT5823, Rp-8-bromo-cGMP) block this upregulation, while 8-bromo-cGMP and cGMP phosphodiesterase inhibitor MY-5445 alone induce CD11b. GSNO-induced CREB activation via PKG was required. Pharmacological inhibitor/activator studies in BV-2 and primary microglial cells, NO donor treatment, in vivo co-microinjection experiments, flow cytometry The Journal of biological chemistry High 16551637
2009 Mac-1 (CD11b/CD18) on recruited neutrophils is a critical molecular link between inflammation and thrombosis in glomerulonephritis. Mac-1-deficient mice show markedly attenuated neutrophil recruitment, endothelial injury, glomerular thrombosis, and acute renal failure. Neutrophil elastase activity is reduced in Mac-1-deficient mice, implicating it as an effector of Mac-1-mediated injury. Mac-1 on neutrophils interacts with glycoprotein Ibα (GPIbα) on platelets; antibody-mediated disruption of this Mac-1–GPIbα interaction attenuates thrombotic glomerulonephritis without affecting renal neutrophil accumulation. Genetic knockout (Mac-1-deficient mice), neutrophil immunodepletion, platelet immunodepletion, antibody-mediated blockade of Mac-1–GPIbα interaction, enzymatic activity assays, histopathology Circulation High 19752320
2012 The lupus-associated rs1143679 (R77H) variant of ITGAM (CD11b) impairs a broad range of CR3 effector functions in human monocytes, including: 31% reduction in phagocytosis of iC3b-opsonized erythrocytes, 24% reduction in adhesion to iC3b, and loss of CR3-ligation-mediated inhibition of TLR7/8-induced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). The functional defect was confirmed by replication in COS7 cells transfected with variant-specific CD11b. No genotype-specific difference in CD11b expression or activation epitope expression was observed. Ex vivo monocytes/macrophages from homozygous WT or 77H donors; phagocytosis assay, adhesion assay, cytokine ELISA after CR3 ligation, conformation-specific antibody staining; COS7 cell transfection with variant-specific CD11b Annals of the rheumatic diseases High 22586164
2013 CD11b negatively regulates B cell receptor (BCR) signaling to maintain autoreactive B cell tolerance. CD11b-deficient autoreactive B cells show hyperproliferative BCR responses and enhanced survival. Mechanistically, CD11b directly binds CD22; in its absence, CD22-SHP-1 recruitment is diminished, leading to decreased Lyn and CD22 phosphorylation and increased calcium influx. The lupus-associated rs1143679 variant of CD11b completely abrogates this regulatory effect on BCR signaling through disruption of CD22-CD11b direct binding. Co-IP demonstrating CD22-CD11b direct binding, BCR crosslinking proliferation assay in CD11b-deficient vs. WT B cells, phosphotyrosine analysis, SHP-1 recruitment assay, calcium flux measurement, transfection of WT and rs1143679 variant CD11b, in vivo BCR engagement in CD11b-/- mice Nature communications High 24264377
2017 CD11b activation suppresses TLR-dependent inflammatory signaling and type I interferon (IFN-I) responses in leukocytes via an AKT/FOXO3/IRF3/IRF7 pathway. Pharmacological activation of CD11b with small molecule agonist LA1 reduces IFN-I responses in WT but not CD11b-deficient mice and protects lupus-prone MRL/Lpr mice from end-organ injury. Three nonsynonymous ITGAM SNPs that reduce CD11b activity are associated with elevated IFN-I in lupus patients. TLR-stimulated macrophages from CD11B SNP carriers show increased basal IRF7 and IFN-β expression and increased nuclear exclusion of FOXO3, all suppressed by LA1. Small molecule CD11b agonist (LA1) treatment, CD11b-deficient mice, lupus-prone mouse model (MRL/Lpr), signaling pathway analysis (AKT/FOXO3/IRF3/7), macrophages from human ITGAM SNP carriers, flow cytometry, ELISA The Journal of clinical investigation High 28263189
2018 CD11b activation promotes pro-inflammatory (M1) macrophage polarization by stimulating expression of microRNA Let-7a. Conversely, CD11b inhibition prevents Let-7a expression and induces cMyc expression, leading to immune-suppressive macrophage polarization, vascular maturation, and accelerated tumor growth. Pharmacological activation of CD11b with small molecule agonist Leukadherin 1 (LA1) promotes pro-inflammatory polarization and suppresses tumor growth. Unexpectedly, CD11b does not regulate myeloid cell recruitment to tumors but controls myeloid cell polarization. CD11b genetic knockout and pharmacological activation (LA1), myeloid cell polarization assays, microRNA expression analysis (Let-7a), cMyc expression measurement, tumor growth models (murine and human cancer xenografts) Nature communications High 30568188
2019 The staphylococcal pore-forming cytotoxin leukocidin GH (LukGH) binds the α-I domain of CD11b with two binding interfaces (on LukG and LukH protomers). Human CD11b-I induces LukGH oligomerization in solution, which is required for cytolytic activity. LukGH binds murine CD11b-I weakly and is inactive toward murine neutrophils. A LukGH variant engineered to bind mouse CD11b-I demonstrated that cytolysis requires both binding and receptor-dependent oligomerization. Crystal structure of LukGH in complex with human and murine CD11b α-I domain, SAXS for oligomerization in solution, engineered LukGH variants with altered CD11b binding specificity, cytolysis assays with murine neutrophils Proceedings of the National Academy of Sciences of the United States of America High 31852826
2018 Integrin CD11b negatively regulates Mincle-mediated macrophage inflammatory signaling via recruitment of a Lyn-SIRPα-SHP1 complex. Upon Mincle activation by mycobacterial cord factor, CD11b is activated and forms a Mincle-CD11b signaling complex. Activated CD11b recruits Lyn, SIRPα, and SHP1, which dephosphorylate Syk to inhibit downstream Mincle-mediated inflammation. CD11b deficiency results in hyperinflammation following mycobacterial infection. Co-immunoprecipitation of Mincle-CD11b complex, CD11b knockout macrophages, phosphorylation assays for Syk, Lyn activator (MLR1023) experiments, mycobacterial infection model Experimental & molecular medicine High 29400702
2015 The heteromeric transcription factor GABP (GABPα/GABPβ1) directly activates the ITGAM/CD11b promoter via three binding sites close to the translational start site, inducing CD11b expression and myeloid differentiation. Demonstrated by luciferase reporter assays, chromatin immunoprecipitation (ChIP), and Shield1-dependent proteotuning. Luciferase promoter reporter assays, chromatin immunoprecipitation (ChIP), Shield1-dependent protein-level tuning, surface marker and morphological analysis of myeloid differentiation, overexpression in U937 cells Biochimica et biophysica acta High 26170143
2016 Folate receptor β (FRβ) interacts with CD11b/CD18 at the plasma membrane of macrophages, impairing CD11b/CD18-mediated adhesion to collagen. FRβ(+) macrophages and FRβ-transduced THP-1 cells show reduced adhesion to collagen compared to FRβ(-) counterparts. FRβ is only expressed by human macrophages differentiated with M-CSF. Affinity purification and mass spectrometric analysis of FRβ protein microenvironment, cell adhesion assay to collagen, FRβ transduction of THP-1 cells, flow cytometry, primary human macrophage differentiation conditions Journal of immunology Medium 27534550
2020 CD11b signaling prevents chondrocyte hypertrophy and mineralization. CD11b-deficient chondrocytes show increased mineralization in vitro (quantified by Alizarin Red), elevated alkaline phosphatase (Alp) expression and activity, enhanced secretion of pro-mineralizing IL-6, and increased ratios of collagen X/collagen II and Runx2/Sox9 (indices of hypertrophy). Addition of anti-IL-6 receptor antibody to CD11b-KO chondrocytes reduces calcification, identifying IL-6 as a downstream mediator. CD11b agonist LA1 reduces chondrocyte mineralization, Alp expression, IL-6 production, and collagen X expression. In the meniscectomy OA model, CD11b deficiency leads to more severe OA. Primary murine CD11b KO chondrocytes, Alizarin Red staining for mineralization, qRT-PCR for gene expression, Alp activity assay, ELISA for IL-6, anti-IL-6R antibody blocking, CD11b agonist LA1, in vivo meniscectomy OA model with OARSI scoring Frontiers in cell and developmental biology High 33392201
2023 Siglec-15 binds integrin CD11b on human T cells as a binding partner. This interaction was identified by co-crystallization and binding studies; Siglec-15 binding to T cells (which lack STn expression) depends on α(2,3)- and α(2,6)-linked sialoglycans and requires CD11b as the receptor. Crystal structure of Siglec-15, STD-NMR spectroscopy for binding mode characterization, molecular dynamics simulations, identification of CD11b as Siglec-15 binding partner on T cells Nature communications High 37311743
2005 CR3 (CD11b/CD18) serves as the receptor for the Bordetella pertussis adhesin filamentous hemagglutinin (FHA) and mediates phagocytosis of B. pertussis. FHA-mediated attachment to CR3 promotes phagocytosis. Anti-CR3 antibody blocks both attachment and phagocytosis. Elevated CR3 surface expression alone (induced by TNF-α, IFN-γ, FHA, or pertussis toxin) is not sufficient to promote phagocytosis; TNF-α increased both CR3 expression and phagocytic capacity, while IFN-γ increased expression without increasing phagocytosis. Adenylate cyclase toxin (ACT) resists phagocytosis independently of CR3 expression level. Anti-CR3 antibody blocking of attachment and phagocytosis, purified FHA/pertussis toxin/ACT treatments, CR3 surface expression measurement, phagocytosis assays with FHA mutants and SphB1 protease mutants Infection and immunity High 16239529
2019 Partial pharmacological activation of CD11b with small molecule agonist ADH-503 repolarizes tumor-associated macrophages, reduces immunosuppressive myeloid cell infiltration in pancreatic tumors, and enhances dendritic cell and antitumor T cell responses, rendering checkpoint inhibitors effective in previously unresponsive PDAC models. Small molecule CD11b agonist (ADH-503) in mouse PDAC models, flow cytometry for myeloid cell polarization and T cell responses, combination with checkpoint inhibitors Science translational medicine Medium 31270275
2017 CD11b regulates the Treg/Th17 balance in murine arthritis via IL-6. CD11b-deficient dendritic cells produce much stronger IL-6 and induce enhanced Th17-cell differentiation compared to WT DCs. Anti-IL-6 receptor antibody treatment in CD11b-/- mice suppressed Th17 induction and reduced arthritis severity. Severe arthritis in CD11b-/- mice was rescued by adoptive transfer of CD11b+ DCs, placing CD11b upstream of IL-6-mediated Th17 differentiation. CD11b knockout mouse arthritis model (CIA), DC co-culture with T cells, IL-6 ELISA, anti-IL-6R antibody treatment, adoptive transfer of CD11b+ DCs European journal of immunology High 28191643
2020 S100A8/A9 (alarmin) is required for upregulation of CD11b specifically on neutrophils during chronic tuberculosis infection, mediating neutrophil accumulation in the lung. S100A8/A9 deficiency results in reduced CD11b expression on neutrophils and impaired neutrophil accumulation, with improved Mycobacterium tuberculosis control during chronic (but not acute) TB. S100A8/A9-deficient mice, TB infection model, neutrophil depletion, flow cytometry for CD11b expression, comparison of acute vs. chronic TB The Journal of clinical investigation Medium 32134742
2014 CD11b is the major complement receptor mediating macrophage adherence to helminth larval surfaces. In vitro coculture of bone marrow-derived macrophages with H. polygyrus bakeri larvae demonstrated that CD11b mediates complement-dependent MΦ adherence. However, larval immobilization was largely independent of CD11b and instead required FcγRI (CD64). In vitro coculture assay of larvae and bone marrow-derived MΦ, CD11b-deficient macrophages, antibody blocking, in vivo challenge infection Journal of immunology Medium 25548226
2020 CD11b on myeloid cells mediates macrophage adhesion and migration to the vasculature during hypertension. CD11b knockout or anti-CD11b antibody treatment attenuates Ang II-induced hypertension, aortic remodeling, superoxide generation, vascular dysfunction, and CD11b+ macrophage infiltration. Wild-type mice reconstituted with CD11b-deficient bone marrow recapitulate these protective effects. Conversely, CD11b agonist LA1 exacerbates hypertensive response. CD11b KO mice, bone marrow chimeras, pharmacological CD11b inhibition (neutralizing antibody) and activation (LA1), Ang II and DOCA-salt hypertension models, macrophage adhesion and migration assays in vitro, flow cytometry, aortic ring analysis Hypertension High 36377602
2023 CD11b mediates hypertensive cardiac remodeling by regulating macrophage infiltration and M1 polarization. CD11b and CD18 are the most highly upregulated integrin subunits in Ang II-infused hearts. CD11b KO or neutralizing antibody treatment attenuates cardiac remodeling and macrophage infiltration/M1 polarization. CD11b agonist LA1 shows opposite (worsening) effects. In vitro, CD11b KO reduces macrophage adhesion and M1 polarization, and reduces paracrine-induced cardiomyocyte enlargement and fibroblast differentiation. CD11b KO mice, bone marrow chimeras, anti-CD11b antibody and LA1 agonist, Ang II and DOCA-salt cardiac remodeling models, in vitro macrophage-cardiomyocyte co-cultures, flow cytometry, histology Journal of advanced research High 36822392
2021 CD11b and the mechanosensitive ion channel Piezo1 engage in crosstalk in macrophages responding to mechanical stretch. Both static and cyclic stretch increase CD11b expression and decrease Piezo1 expression. siRNA knockdown of CD11b abrogates stretch-mediated changes in inflammatory responses. Knockdown of CD11b enhances Piezo1 expression, and conversely knockdown of Piezo1 enhances CD11b expression, indicating reciprocal regulation. Stretch-mediated macrophage activation changes are dependent on actin polymerization. Static and cyclic uniaxial stretch apparatus, siRNA knockdown of CD11b and Piezo1, cytokine response assays (IFNγ/LPS and IL4/IL13 stimulation), actin polymerization inhibitor (pharmacological), flow cytometry for CD11b expression Frontiers in immunology Medium 34630381
2020 CD154 (CD40L) can bind CD11b as an alternate receptor during alloimmunity, distinct from the classical CD154-CD40 interaction. A peptide antagonist that specifically blocks CD154-CD11b interaction (without affecting CD154-CD40) significantly increased allograft survival when combined with anti-CD40 antibody, and reduced graft-infiltrating CD8+ T cells and innate immune cells. CD154-CD11b antagonism was more effective than CD40 blockade alone. Fully allogeneic murine transplant model, CD40-/- hosts, CD154-CD11b-specific peptide antagonist, antibody blockade of CD40, flow cytometry for graft-infiltrating cells American journal of transplantation Medium 32149455

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 751 23352232
2009 Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution. Blood 356 19346498
2007 CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 298 17911608
2021 Type I interferon activates MHC class I-dressed CD11b+ conventional dendritic cells to promote protective anti-tumor CD8+ T cell immunity. Immunity 291 34800368
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2008 Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils. Laboratory investigation; a journal of technical methods and pathology 183 18762778
2015 CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity. Proceedings of the National Academy of Sciences of the United States of America 166 26598697
2019 Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies. Science translational medicine 159 31270275
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2021 Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues. Frontiers in immunology 67 34630381
2012 The rs1143679 (R77H) lupus associated variant of ITGAM (CD11b) impairs complement receptor 3 mediated functions in human monocytes. Annals of the rheumatic diseases 64 22586164
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2002 Neutrophils CD11b and fibroblasts PGE(2) are elevated in Alzheimer's disease. Neurobiology of aging 62 12009501
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2018 PDL2+ CD11b+ dermal dendritic cells capture topical antigen through hair follicles to prime LAP+ Tregs. Nature communications 60 30531969
2015 Mouse CD11b+Kupffer Cells Recruited from Bone Marrow Accelerate Liver Regeneration after Partial Hepatectomy. PloS one 60 26333171
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2013 Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. PloS one 30 24204843
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2017 CD11b and CD200 on Circulating Monocytes Differentiate Two Angiographic Subtypes of Polypoidal Choroidal Vasculopathy. Investigative ophthalmology & visual science 27 29049725
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2007 Increased CD11b expression on polymorphonuclear leucocytes and cytokine profiles in patients with Kawasaki disease. Clinical and experimental immunology 24 17286760
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