Affinage

ICAM3

Intercellular adhesion molecule 3 · UniProt P32942

Length
547 aa
Mass
59.5 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ICAM-3 (CD50) is an immunoglobulin superfamily adhesion molecule constitutively expressed on leukocytes that functions as a principal ligand for LFA-1 (αLβ2) and αDβ2 integrins, and for the C-type lectin DC-SIGN, thereby orchestrating leukocyte adhesion, T cell co-stimulation, dendritic cell–T cell contact, and apoptotic cell clearance. LFA-1 binds ICAM-3 through its I domain at residues distributed across both the ABED and GFC faces of Ig domain 1, a binding mode distinct from that used for ICAM-1; this interaction mediates outside-in signaling that activates Src-family kinases (p56lck, p59fyn, hck, lyn), PKC, and tyrosine phosphorylation cascades regulated by the CD45 phosphatase, resulting in calcium mobilization, cytoskeletal reorganization, integrin avidity upregulation, and T cell co-stimulation (PMID:1448173, PMID:7905020, PMID:7515097, PMID:7520448, PMID:9686599). ICAM-3 concentrates at the T cell uropod and the initial T cell–APC contact zone to promote early antigen-independent adhesion and signaling prior to immunological synapse formation, and DC-SIGN on dendritic cells engages Lewis x glycans on ICAM-3 to stabilize this contact (PMID:7525599, PMID:11812993, PMID:10721994, PMID:17145745). On apoptotic leukocytes, ICAM-3 undergoes an altered-recognition switch from LFA-1 to macrophage CD14, functioning as an eat-me signal that promotes phagocytosis and releases ICAM-3-bearing microparticles that attract macrophages; additionally, in cancer cells, intracellular ICAM-3 recruits Src via its YLPL motif and signals through PI3K–AKT to drive migration, invasion, and stemness maintenance (PMID:10352301, PMID:22117198, PMID:29477378, PMID:29729315).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 High

    Identification of ICAM-3 as a third LFA-1 ligand on leukocytes established a new adhesion molecule in the immunoglobulin superfamily with distinct expression and potential function from ICAM-1 and ICAM-2.

    Evidence Two independent groups expression-cloned ICAM-3 cDNA and demonstrated LFA-1-dependent adhesion in functional assays

    PMID:1448173 PMID:1448174

    Open questions at the time
    • Binding-site residues on ICAM-3 not yet mapped
    • Signaling consequences of engagement unknown
    • Relationship to CDw50 antigen not formally proven
  2. 1992 High

    Demonstration that ICAM-3 cytoplasmic domain undergoes rapid PKC-dependent serine phosphorylation revealed that ICAM-3 is a regulated signaling-competent molecule, not merely a passive adhesion scaffold.

    Evidence 32P-radiolabeling and phosphoamino acid analysis of immunoprecipitated ICAM-3 with PKC activators and inhibitors

    PMID:1730238

    Open questions at the time
    • Specific serine residues not identified
    • Functional consequence of phosphorylation not determined
  3. 1993 High

    Localization of ICAM-3 to the T cell uropod and demonstration that its engagement enhances LFA-1 avidity for ICAM-1 established ICAM-3 as an active regulator of integrin-mediated adhesion rather than simply a redundant LFA-1 counter-receptor.

    Evidence Immunofluorescence microscopy of T lymphoblasts combined with mAb blocking experiments and adhesion assays

    PMID:7901223 PMID:8223855

    Open questions at the time
    • Mechanism linking ICAM-3 engagement to integrin activation not defined
    • Whether co-stimulatory function requires uropod localization unknown
  4. 1994 High

    A wave of signaling studies revealed that ICAM-3 engagement triggers tyrosine phosphorylation, calcium flux, and association with Src-family kinases (p56lck, p59fyn in T cells; hck, lyn in neutrophils), with CD45 phosphatase serving as a negative regulator — defining ICAM-3 as a bona fide outside-in signaling receptor.

    Evidence Co-immunoprecipitation of kinases with ICAM-3, in vitro kinase assays, phosphotyrosine blotting, calcium flux measurements, and CD45 mAb/inhibitor blocking in T cells and neutrophils

    PMID:7515097 PMID:7520448 PMID:7876557

    Open questions at the time
    • Direct phosphorylation substrates downstream of Src kinases not identified
    • Whether kinase association is direct or scaffolded unknown
  5. 1994 High

    Mapping the LFA-1 binding site to Ig domain 1 of ICAM-3 and defining key contact residues (E37, T38, Q75) by mutagenesis and electron microscopy provided the first structural framework for ICAM-3–LFA-1 interaction.

    Evidence Site-directed mutagenesis of domain 1, LFA-1 adhesion assays, domain deletion/chimera analysis, electron microscopy showing 15 nm rod

    PMID:7531103 PMID:7905020 PMID:8798624

    Open questions at the time
    • No crystal structure of ICAM-3 domain 1 or ICAM-3–I domain complex
    • Role of glycosylation in LFA-1 binding not addressed
  6. 1994 High

    Discovery of proteolytic shedding of ICAM-3 from activated neutrophils and detection of soluble ICAM-3 in plasma identified a regulatory mechanism for surface ICAM-3 levels with potential immunomodulatory function.

    Evidence 125I-radiolabel internalization assay, immunoprecipitation of supernatants, radioimmunoassay of plasma, protease inhibitor treatment

    PMID:7525295

    Open questions at the time
    • Identity of the protease(s) responsible for shedding not determined
    • Functional role of soluble ICAM-3 in vivo unclear
  7. 1995 High

    Identification of αDβ2 as a second integrin receptor preferring ICAM-3 over ICAM-1 expanded the functional repertoire of ICAM-3 beyond LFA-1, while Mac-1 and p150,95 were excluded as ICAM-3 receptors.

    Evidence Transfection of αD cDNA with adhesion assays comparing ICAM-1 vs ICAM-3; purified Mac-1 adhesion assays with ICAM-3 transfectants

    PMID:7737271 PMID:8777714

    Open questions at the time
    • Physiological context for αDβ2–ICAM-3 interaction not defined
    • Whether αDβ2 and LFA-1 compete for the same ICAM-3 binding site unknown
  8. 1998 High

    Refined mutagenesis revealed that LFA-1 contacts both the ABED and GFC faces of ICAM-3 domain 1, unlike ICAM-1 where only the GFC face is used, establishing a structurally distinct binding mode that explains selective antibody blocking patterns.

    Evidence Systematic point mutagenesis of 18 residues in domain 1 combined with LFA-1 adhesion assays and mAb mapping

    PMID:9686599

    Open questions at the time
    • No co-crystal structure to confirm dual-face binding model
    • Conformational dynamics of the interaction not addressed
  9. 1999 High

    The discovery that ICAM-3 on apoptotic leukocytes shifts from an LFA-1 ligand to a macrophage CD14 ligand established ICAM-3 as a phagocytic recognition ('eat-me') signal, revealing a non-adhesion function for this molecule.

    Evidence mAb blockade of macrophage–apoptotic cell interactions, ICAM-3 transfection into non-leukocyte cells, multiple apoptotic stimuli

    PMID:10352301

    Open questions at the time
    • Nature of the molecular change on ICAM-3 during apoptosis not defined
    • Whether glycan modification mediates the ligand switch unknown
  10. 2000 High

    Identification of DC-SIGN as a high-affinity ICAM-3 receptor on dendritic cells established a new axis for antigen-independent DC–T cell contact that initiates the immunological synapse.

    Evidence Binding assays and mAb inhibition of DC-SIGN–ICAM-3 interaction blocking DC-induced T cell proliferation

    PMID:10721994

    Open questions at the time
    • Relative contributions of DC-SIGN vs LFA-1 to DC–T cell adhesion not quantified
    • Downstream signaling in DC upon DC-SIGN–ICAM-3 engagement not characterized
  11. 2002 High

    Live-cell imaging demonstrated that ICAM-3 clusters at the initial T cell–APC contact zone before antigen recognition, positioning it as a key molecule in pre-immunological synapse formation and early signaling.

    Evidence Time-lapse live-cell imaging of T cell–APC conjugate formation with mAb blocking and cytoskeletal analysis

    PMID:11812993

    Open questions at the time
    • Molecular mechanism driving ICAM-3 clustering to the contact zone not identified
    • Whether ICAM-3 clustering requires DC-SIGN engagement or LFA-1 engagement unclear
  12. 2006 High

    Demonstration that DC-SIGN recognizes Lewis x glycan structures on ICAM-3 (synthesized by FUT IX) resolved the glycan basis of the DC-SIGN–ICAM-3 interaction and explained cell-type-specific binding (granulocyte ICAM-3 binds DC-SIGN, other leukocyte ICAM-3 does not).

    Evidence MALDI-TOF mass spectrometry of ICAM-3 glycans, FUT cotransfection experiments, anti-Lewis x mAb blocking, DC-SIGN binding assays

    PMID:17145745

    Open questions at the time
    • Whether Lewis x on T cell ICAM-3 is regulated during activation unknown
    • Structural basis of DC-SIGN selectivity for Lewis x on ICAM-3 vs other glycoproteins not resolved
  13. 2011 High

    Demonstration that apoptotic cells release ICAM-3-bearing microparticles that serve as macrophage chemoattractants extended the eat-me signal concept to a 'find-me' signal, showing ICAM-3 domains 1–2 mediate both tethering and chemotaxis.

    Evidence ICAM-3-deficient apoptotic leukocytes, microparticle isolation, chemotaxis and phagocytosis assays with blocking and non-blocking mAbs

    PMID:22117198

    Open questions at the time
    • Receptor on macrophages mediating ICAM-3-microparticle chemotaxis not definitively identified
    • Whether soluble shed ICAM-3 and microparticle-bound ICAM-3 have overlapping or distinct functions unclear
  14. 2018 Medium

    In cancer cells, ICAM-3 was shown to recruit Src kinase via the intracellular YLPL motif and activate PI3K–AKT signaling to maintain stemness (SOX2/OCT4) and drive metastasis through ERM-scaffold-dependent lamellipodia formation, extending ICAM-3 function beyond immune adhesion.

    Evidence Co-immunoprecipitation of ICAM-3 with Src and ERM proteins, PI3K/Src inhibitor treatment, intracellular/extracellular domain mutants, in vivo tumor and metastasis models

    PMID:29477378 PMID:29729315

    Open questions at the time
    • Cancer-related findings from single laboratories, not independently confirmed
    • Whether YLPL-Src and ERM interactions occur simultaneously or are context-dependent unknown
    • Relevance of these mechanisms to normal leukocyte biology not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • No atomic-resolution structure of ICAM-3 (alone or in complex with LFA-1, DC-SIGN, or CD14) exists, and the molecular basis of the apoptotic ligand switch from LFA-1 to CD14 remains undefined.
  • No crystal or cryo-EM structure of ICAM-3 or its complexes
  • Mechanism of ICAM-3 modification during apoptosis unknown
  • Identity of the sheddase(s) cleaving ICAM-3 from neutrophils not determined
  • In vivo phenotype of ICAM-3 deficiency in humans or knockout animals not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 7 GO:0060089 molecular transducer activity 4 GO:0048018 receptor ligand activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-1500931 Cell-Cell communication 5 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 3
Partners
CD14CD209EZRFYNITGALITGB2LCKMSN

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 ICAM-3 (ICAM-R/CDw50) was identified as a third ligand for LFA-1 (CD11a/CD18), consisting of five immunoglobulin superfamily domains, constitutively expressed on all leukocytes, binding LFA-1 through its two N-terminal domains. Expression cloning of cDNA, functional adhesion assays with LFA-1 Nature High 1448173 1448174
1993 ICAM-3 and CDw50 are the same glycoprotein (~120 kDa), confirmed by immunochemical, functional, and peptide sequencing studies. Immunoprecipitation, peptide sequencing, functional assays European journal of immunology High 8325327
1993 ICAM-3 is located at cellular uropods of T lymphoblasts and regulates the LFA-1/ICAM-1 adhesion pathway; engagement of ICAM-3 with activating mAb induces T cell aggregation dependent on LFA-1/ICAM-1 and enhances LFA-1 avidity for ICAM-1. Immunofluorescence microscopy, mAb blocking experiments, T lymphoblast adhesion assays The Journal of cell biology High 7901223
1993 ICAM-3 acts as a co-stimulatory molecule for both resting and activated T lymphocytes; soluble purified ICAM-3 co-immobilized with anti-CD3 stimulated T lymphocyte activation (CD25 and CD69 expression), and this effect was blocked by anti-CD18, implicating LFA-1 as the mediating beta2 integrin. Immunoaffinity purification of ICAM-3, T cell co-stimulation assays, mAb blocking European journal of immunology High 8223855
1994 The LFA-1 binding site on ICAM-3 resides in immunoglobulin domain 1; purified ICAM-3 supports LFA-1-dependent adhesion in a temperature- and cation-dependent manner, and two ICAM-3 mAbs (CBR-IC3/1 and CBR-IC3/2) together are required to fully block LFA-1-dependent adhesion. ICAM-3 also provides a costimulatory proliferative signal to resting T lymphocytes. Adhesion assays with purified ICAM-3, mAb blocking, T cell proliferation assays The Journal of experimental medicine High 7905020
1994 ICAM-3 engagement induces tyrosine phosphorylation of proteins (125, 70, and 38 kDa), and this signaling is regulated by the CD45 tyrosine phosphatase; inhibitors of tyrosine kinase activity and certain anti-CD45 mAbs abolished ICAM-3-mediated cell aggregation. Western blot for phosphotyrosine, immunofluorescence, inhibitor studies, mAb blocking The Journal of cell biology High 7520448
1994 The LFA-1 I domain contains the binding site for ICAM-3; two anti-LFA-1 mAbs (YTH81.5 and 122.2A5) with I domain epitopes selectively block adhesion to ICAM-3 but not ICAM-1, demonstrating that LFA-1 binds ICAM-1 and ICAM-3 in a selective manner using the I domain. T cell adhesion assays to immobilized ligands, mAb epitope mapping, COS cell transfection adhesion assays The Journal of cell biology High 7518468
1994 ICAM-3 engagement by activating mAb HP2/19 regulates T lymphocyte morphology, induces a heading uropod-like structure where ICAM-3 concentrates distally, and enhances integrin-mediated (LFA-1, VLA-4, VLA-5) T cell adhesion to endothelial cells and extracellular matrix ligands. Immunofluorescence microscopy, T cell adhesion assays to ICAM-1, VCAM-1, fibronectin fragments, mAb blocking The Journal of cell biology High 7525599
1994 CDw50/ICAM-3 cross-linking on Jurkat T cells induces calcium mobilization dependent on extracellular Ca2+ uptake and tyrosine phosphorylation, and p56lck and p59fyn protein tyrosine kinases are physically associated with ICAM-3 (co-immunoprecipitation). Calcium flux assays, in vitro kinase assays, immunoprecipitation with specific antisera for p56lck and p59fyn The Journal of experimental medicine High 7515097
1994 ICAM-3 surface expression on neutrophils is down-regulated by a proteolytic shedding mechanism upon activation (PMA or calcium ionophore), releasing soluble ICAM-3 into the medium; protease inhibitors abrogate this down-regulation. A soluble form of ICAM-3 is detectable in plasma of healthy humans. 125I-anti-ICAM-3 internalization assay, immunoprecipitation of cell-free supernatants, radioimmunoassay of plasma, protease inhibitor treatment European journal of immunology High 7525295
1994 ICAM-3 (CD50) signaling through CD50 increases beta1 and beta2 integrin avidity (not surface expression) to enhance T lymphocyte adhesion to TNF-stimulated endothelial cells and extracellular matrix proteins, demonstrated by combined blocking of both integrin families. T cell adhesion assays to endothelial cells and ECM, mAb blocking of integrin chains, flow cytometry for integrin surface expression European journal of immunology High 7515813
1994 ICAM-3 on neutrophils is phosphorylated predominantly on tyrosine residues, and protein tyrosine kinase activity (including hck and lyn src-family kinases) is associated with CD50 in immunoprecipitates from human neutrophils. Radiolabeling, immunoprecipitation, phosphoamino acid analysis, in vitro kinase assay Journal of immunology High 7876557
1994 The LFA-1 binding site on ICAM-3 involves a conserved integrin-binding motif in domain 1 including residues E37/T38, and Q75 (conserved in ICAM-1 and ICAM-2) confers specificity; electron microscopy shows ICAM-3 is a straight rod of 15 nm consistent with head-to-tail Ig domain arrangement. Electron microscopy, site-directed mutagenesis of ICAM-3, LFA-1-dependent adhesion assays Cell adhesion and communication High 7531103
1995 Alpha-d/CD18 (alphaDbeta2), a fourth beta2 integrin, binds ICAM-3 preferentially over ICAM-1, identifying ICAM-3 as a preferred ligand for this integrin. Transfection of alpha-d cDNA, adhesion assays comparing ICAM-1 vs. ICAM-3 Immunity High 8777714
1995 ICAM-3 interacts with Mac-1 (CD11b) or p150,95 (CD11c) neither from lymphoid cells nor from neutrophils; purified Mac-1 does not support adhesion of ICAM-3-expressing transfectants, establishing ICAM-3 as not a counter-receptor for Mac-1 or p150,95. CHO cell transfection adhesion assays with purified Mac-1, L cell transfectants European journal of immunology High 7737271
1996 The LFA-1 binding site on ICAM-3 maps exclusively to domain 1; deletion of individual Ig domains and chimeras with CD21 showed domain 1 is necessary and sufficient, and point mutagenesis identified five contact residues (Asn23, Ser25, Glu37, Phe54, Gln75) predicted to cluster on the BED face and C/E/FG regions of domain 1. Domain deletion mutagenesis, ICAM-3/CD21 chimeras, point mutagenesis (45 mutants), LFA-1 adhesion assays, mAb epitope mapping The Journal of biological chemistry High 8798624
1997 The LFA-1 I domain acts as a transient, Mg2+-dependent binding module for ICAM-3 in hydrodynamic flow; GPI-anchored I domain cells roll on ICAM-3 bilayers, and the LFA-1-activating antibody MEM-83 (which stimulates ICAM-1 binding) blocks interaction with ICAM-3, demonstrating distinct modes of I domain interaction with ICAM-1 vs. ICAM-3. GPI-anchored I domain cell expression, flow chamber rolling assays on lipid bilayers with purified ICAM-1/ICAM-3 The Journal of experimental medicine High 9271587
1998 The LFA-1 binding site on ICAM-3 domain 1 includes residues on both the ABED face and the GFC face, unlike ICAM-1 where only GFC face residues interact with LFA-1; mutagenesis of 18 positions identified 7 residues reducing or abolishing LFA-1 adhesion. Point mutagenesis of 18 residues in domain 1, LFA-1 adhesion assays, mAb blocking studies Journal of immunology High 9686599
1998 Engagement of ICAM-3 by a mAb recognizing the alphaLbeta2-binding region activates PMN homotypic aggregation through outside-in signaling: activating tyrosine kinase and PKC, reorganizing the cytoskeleton, and activating constitutive surface beta2 integrins without inducing degranulation or beta2 integrin recruitment. mAb engagement (Fab and F(ab')2 fragments), aggregation assays, kinase activity measurements, cytoskeletal reorganization assays Journal of immunology High 9834117
1998 Co-engagement of ICAM-3 (domain 1 epitopes) with Fc receptors (FcgammaRI or FcgammaRII) on monocytes is required for maximal chemokine secretion (MIP-1alpha, IL-8, MCP-1); ICAM-3 engagement also induces monocyte spreading via direct outside-in signaling (Fab/F(ab')2-dependent). Immobilized mAb engagement, Fab/F(ab')2 fragments, chemokine ELISA, microscopy for cell spreading Journal of immunology High 9605163
1999 ICAM-3 on apoptotic leukocytes acts as a phagocytic recognition signal for macrophages; the first Ig-like domain of ICAM-3 mediates macrophage recognition, and its binding preference shifts from LFA-1 to macrophage CD14 during apoptosis, enabling phagocytosis. mAb blockade of macrophage-apoptotic cell interactions, ICAM-3 transfection into non-leukocytes, apoptosis triggered by multiple stimuli Journal of immunology High 10352301
2000 DC-SIGN, a DC-specific C-type lectin, binds ICAM-3 expressed on resting T cells with high affinity to mediate transient DC-T cell adhesion; anti-DC-SIGN antibodies inhibit DC-induced proliferation of resting T cells, indicating DC-SIGN/ICAM-3 stabilizes the DC-T cell contact zone. Binding assays, mAb inhibition of DC-T cell interaction and T cell proliferation, expression analysis of DC-SIGN on DC in vitro and in vivo Cell High 10721994
2000 LFA-1 (alphaLbeta2) preferentially binds ICAM-3 as its primary ligand supporting neutrophil homotypic adhesion at higher shear rates (>300 s-1), whereas Mac-1 is the predominant integrin at lower shear rates (~100 s-1); the contributions of LFA-1 and Mac-1 to ICAM-3-dependent aggregation are regulated by shear magnitude and stimulus duration. Cone-plate viscometer shear experiments, mAb blocking with panel of anti-LFA-1, anti-Mac-1, and anti-ICAM-3 antibodies, flow cytometry for aggregate formation kinetics Journal of immunology High 10725740
2001 ICAM-3 N-linked oligosaccharides are mainly of tri- and tetra-antennary complex-type (~60% containing poly N-acetyllactosamine chains with type 1 structure), with a small amount of high-mannose type; approximately 6 mol oligosaccharides per mol ICAM-3. Hydrazinolysis to release N-glycans, paper electrophoresis, lectin column chromatography, sequential exo/endo-glycosidase digestion, methylation analysis European journal of biochemistry High 11179968
2002 ICAM-3 is specifically clustered at the region of the T lymphocyte surface that initiates contact with APCs (pre-immunological synapse), as shown by time-lapse imaging; ICAM-3 promotes early intracellular signaling and cytoskeletal rearrangement before antigen recognition. Time-lapse live-cell imaging, mAb blocking, analysis of T cell-APC conjugate formation, signaling and cytoskeletal assays Nature immunology High 11812993
2006 DC-SIGN binds ICAM-3 from granulocytes via Lewis x glycan residues on ICAM-3; fucosyltransferase IX (FUT IX) is the main enzyme mediating Lewis x synthesis on ICAM-3, with FUT IV contributing to a lesser extent. ICAM-3 from granulocytes but not other leukocytes binds DC-SIGN. Recombinant DC-SIGN binding assays, anti-Lewis x mAbs, MALDI-TOF mass spectrometry, cotransfection studies with multiple FUTs, DC-SIGN-expressing immature DC binding experiments Glycobiology High 17145745
2010 ICAM-3 stimulates cancer cell migration and invasion via an ICAM-3/Akt/CREB/MMP pathway; ICAM-3 overexpression increases Akt phosphorylation, activates CREB, and upregulates MMP-2 and MMP-9 expression and activity, leading to enhanced migration/invasion independent of p53 and PTEN status. Stable ICAM-3-overexpressing transfectants, migration/invasion assays, Akt inhibitor treatment, siRNA knockdown of CREB, gelatin zymography for MMP activity International journal of oncology Medium 19956847
2011 Apoptotic cell-derived ICAM-3 promotes macrophage chemoattraction via ICAM-3-bearing microparticles released during apoptosis; ICAM-3 on apoptotic cells mediates domain 1-2-dependent tethering to macrophages. ICAM-3-deficient microparticles show profound defect in chemotaxis. Novel anti-ICAM-3 mAbs (blocking and non-blocking), ICAM-3-deficient apoptotic leukocytes, microparticle isolation, chemotaxis assays, phagocytosis assays Cell death and differentiation High 22117198
2012 The RUNX3 transcription factor negatively regulates ICAM-3 gene expression; ICAM-3 promoter activity depends on RUNX binding sites, and siRNA-mediated reduction of RUNX3 increases ICAM-3 mRNA; ICAM-3 levels decrease during monocyte-to-macrophage differentiation correlating with increased RUNX3. Promoter-reporter assays, chromatin immunoprecipitation (RUNX binding in vivo), siRNA knockdown of RUNX3, protein level analysis during macrophage differentiation PloS one High 22479382
2013 ICAM-3 and LFA-1 act as recognition receptors in phagocytosis portals of macrophages for engulfment of apoptotic neutrophils; ICAM-3 on macrophages is upregulated upon exposure to apoptotic neutrophils, blocking ICAM-3 on macrophages or apoptotic neutrophils reduces phagocytosis, and ICAM-3/LFA-1 co-localize in phagocytic portals. Gene silencing (siRNA), blocking antibodies, fluorescence microscopy, phagocytosis quantification Apoptosis High 23775590
2018 ICAM-3 recruits and binds Src kinase through the YLPL motif in its intracellular domain, activating PI3K-AKT phosphorylation cascades that enhance SOX2 and OCT4 activity to maintain cancer cell stemness; p-AKT also facilitates p50 nuclear translocation which feeds back to enhance ICAM-3 expression by binding its promoter. siRNA screen, co-immunoprecipitation of ICAM-3 with Src, PI3K/Src inhibitor treatment, in vivo tumor and metastasis models with shICAM-3 cells Cancer letters Medium 29477378
2018 ICAM-3 mediates tumor metastasis via a LFA-1-ICAM-3-ERM-dependent mechanism; ICAM-3 binds LFA-1 through its extracellular domain and ERM scaffold proteins and lamellipodia through its intracellular domain, creating tension that facilitates cell motility; extracellular or intracellular mutants of ICAM-3 abolish metastasis, and LFA-1 antibody or Lifitegrast inhibit ICAM-3-LFA-1-mediated metastasis. ICAM-3 extracellular/intracellular domain mutants, co-immunoprecipitation with ERM proteins, in vitro and in vivo metastasis assays, LFA-1 antibody treatment Biochimica et biophysica acta. Molecular basis of disease Medium 29729315
1992 ICAM-3 (CDw50) is constitutively non-phosphorylated at baseline but becomes rapidly phosphorylated on serine residues within 1–5 minutes upon stimulation with protein kinase C activators (PMA, PDB, mezerein), and PKC inhibitors (staurosporine, H-7) reduce this phosphorylation, implicating PKC-mediated mechanisms in ICAM-3 phosphorylation. Radiolabeling (32P), immunoprecipitation, phosphoamino acid analysis, PKC inhibitor treatment European journal of biochemistry High 1730238
2004 Activation of ICAM-3 on human bone marrow endothelial cells by crosslinking with specific antibodies causes loss of endothelial cell-cell contacts and drop in electrical resistance; biochemical analysis reveals ICAM-3 associates with moesin (and later ezrin) upon crosslinking, and induces production of reactive oxygen species (ROS) that mediate endothelial permeability. ICAM-3 crosslinking, electrical resistance measurement of endothelial monolayers, immunocytochemistry, co-immunoprecipitation of moesin/ezrin with ICAM-3, ROS measurement Journal of vascular research Medium 14726630
2011 Kidins220/ARMS protein co-immunoprecipitates with ICAM-3 and co-localizes at the uropod of polarized T lymphocytes; disruption of cell polarity (PKC-dependent) impairs Kidins220/ARMS association with ICAM-3; Kidins220/ARMS knockdown promotes T cell migration, identifying it as a uropod regulator linked to ICAM-3. Co-immunoprecipitation, immunofluorescence microscopy in polarized T cells, siRNA knockdown, directed migration assays European journal of immunology Medium 21381019

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 1336 10721994
2003 Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO reports 383 12783086
1992 Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes. Nature 322 1448173
1995 A novel leukointegrin, alpha d beta 2, binds preferentially to ICAM-3. Immunity 224 8777714
1992 Cloning and characterization of a new intercellular adhesion molecule ICAM-R. Nature 198 1448174
1994 Characterization of the function of intercellular adhesion molecule (ICAM)-3 and comparison with ICAM-1 and ICAM-2 in immune responses. The Journal of experimental medicine 155 7905020
1993 ICAM-3 interacts with LFA-1 and regulates the LFA-1/ICAM-1 cell adhesion pathway. The Journal of cell biology 150 7901223
1994 Differential distribution of intercellular adhesion molecules (ICAM-1, ICAM-2, and ICAM-3) and the MS-1 antigen in normal and diseased human synovia. Their possible pathogenetic and clinical significance in rheumatoid arthritis. Arthritis and rheumatism 133 8129777
1999 Macrophage recognition of ICAM-3 on apoptotic leukocytes. Journal of immunology (Baltimore, Md. : 1950) 125 10352301
2002 Role of ICAM-3 in the initial interaction of T lymphocytes and APCs. Nature immunology 122 11812993
1995 The increased expression of adhesion molecules ICAM-3, E- and P-selectins on breast cancer endothelium. The Journal of pathology 119 8568591
2002 Functional evaluation of DC-SIGN monoclonal antibodies reveals DC-SIGN interactions with ICAM-3 do not promote human immunodeficiency virus type 1 transmission. Journal of virology 103 12021323
1994 Induction of tyrosine phosphorylation during ICAM-3 and LFA-1-mediated intercellular adhesion, and its regulation by the CD45 tyrosine phosphatase. The Journal of cell biology 98 7520448
2010 Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFN{gamma}: role of CD18, ICAM-1, and ICAM-3. Blood 89 21098395
2011 Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells. Cell death and differentiation 88 22117198
1993 ICAM-3, the third LFA-1 counterreceptor, is a co-stimulatory molecule for both resting and activated T lymphocytes. European journal of immunology 88 8223855
2009 Human milk oligosaccharides reduce HIV-1-gp120 binding to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN). The British journal of nutrition 86 19230080
2006 The location of asparagine-linked glycans on West Nile virions controls their interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin). The Journal of biological chemistry 85 17001080
1994 Involvement of the "I" domain of LFA-1 in selective binding to ligands ICAM-1 and ICAM-3. The Journal of cell biology 82 7518468
2004 Dynamic populations of dendritic cell-specific ICAM-3 grabbing nonintegrin-positive immature dendritic cells and liver/lymph node-specific ICAM-3 grabbing nonintegrin-positive endothelial cells in the outer zones of the paracortex of human lymph nodes. The American journal of pathology 78 15111305
2010 ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB. International journal of oncology 75 19956847
2000 Changed colonic profile of P-selectin, platelet-endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and ICAM-3 in inflammatory bowel disease. Clinical and experimental immunology 75 10931137
1994 ICAM-3 regulates lymphocyte morphology and integrin-mediated T cell interaction with endothelial cell and extracellular matrix ligands. The Journal of cell biology 73 7525599
2010 Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells. The Journal of biological chemistry 72 20080962
1994 CD50 (intercellular adhesion molecule 3) stimulation induces calcium mobilization and tyrosine phosphorylation through p59fyn and p56lck in Jurkat T cell line. The Journal of experimental medicine 65 7515097
2005 Specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcus pneumoniae infection. European journal of immunology 61 16134084
1997 The lymphocyte function-associated antigen 1 I domain is a transient binding module for intercellular adhesion molecule (ICAM)-1 and ICAM-3 in hydrodynamic flow. The Journal of experimental medicine 57 9271587
1997 RANTES stimulation of T lymphocyte adhesion and activation: role for LFA-1 and ICAM-3. European journal of immunology 54 9174593
1994 Signaling through CD50 (ICAM-3) stimulates T lymphocyte binding to human umbilical vein endothelial cells and extracellular matrix proteins via an increase in beta 1 and beta 2 integrin function. European journal of immunology 54 7515813
1995 Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon. Clinical and experimental immunology 53 7542573
2011 Retagging identifies dendritic cell-specific intercellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) protein as a novel receptor for a major allergen from house dust mite. The Journal of biological chemistry 50 22205703
2004 DC-SIGN binds to HIV-1 glycoprotein 120 in a distinct but overlapping fashion compared with ICAM-2 and ICAM-3. The Journal of biological chemistry 50 14970226
1994 Expression of ICAM-R (ICAM-3), a novel counter-receptor for LFA-1, in rheumatoid and nonrheumatoid synovium. Comparison with other adhesion molecules. Arthritis and rheumatism 45 7516162
1995 Circulating forms of ICAM-3 (cICAM-3). Elevated levels in autoimmune diseases and lack of association with cICAM-1. Journal of immunology (Baltimore, Md. : 1950) 44 7836774
1994 Intercellular adhesion molecules (ICAM)-1 ICAM-2 and ICAM-3 function as counter-receptors for lymphocyte function-associated molecule 1 in human immunodeficiency virus-mediated syncytia formation. European journal of immunology 44 7916296
1999 Human T-cell leukaemia/lymphoma virus type 1 syncytium formation is regulated in a cell-specific manner by ICAM-1, ICAM-3 and VCAM-1 and can be inhibited by antibodies to integrin beta2 or beta7. The Journal of general virology 43 10374960
1999 Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3. European journal of immunology 43 10427988
2000 Shear and time-dependent changes in Mac-1, LFA-1, and ICAM-3 binding regulate neutrophil homotypic adhesion. Journal of immunology (Baltimore, Md. : 1950) 42 10725740
1996 Localization of the binding site on intercellular adhesion molecule-3 (ICAM-3) for lymphocyte function-associated antigen 1 (LFA-1). The Journal of biological chemistry 41 8798624
1994 Regulation of ICAM-3 (CD50) membrane expression on human neutrophils through a proteolytic shedding mechanism. European journal of immunology 40 7525295
1993 CDw50 and ICAM-3: two names for the same molecule. European journal of immunology 40 8325327
2007 Investigation of promoter variations in dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) (CD209) and their relevance for human cytomegalovirus reactivation and disease after allogeneic stem-cell transplantation. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 37 18076668
2005 The changes in expression of ICAM-3, Ki-67, PCNA, and CD31 in psoriatic lesions before and after methotrexate treatment. Archives of dermatological research 37 16215763
2018 ICAM3 mediates inflammatory signaling to promote cancer cell stemness. Cancer letters 36 29477378
2013 Novel role of ICAM3 and LFA-1 in the clearance of apoptotic neutrophils by human macrophages. Apoptosis : an international journal on programmed cell death 36 23775590
1995 CD50 (ICAM-3) is phosphorylated on tyrosine and is associated with tyrosine kinase activity in human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 35 7876557
2007 Structural requirements for multimerization of the pathogen receptor dendritic cell-specific ICAM3-grabbing non-integrin (CD209) on the cell surface. The Journal of biological chemistry 34 18073208
2005 Increased expression of ICAM-3 is associated with radiation resistance in cervical cancer. International journal of cancer 32 15880373
2012 RUNX3 regulates intercellular adhesion molecule 3 (ICAM-3) expression during macrophage differentiation and monocyte extravasation. PloS one 31 22479382
1994 Cellular distribution of human leucocyte adhesion molecule ICAM-3. Journal of clinical pathology 31 8132828
2002 Binding of LFA-1 (CD11a) to intercellular adhesion molecule 3 (ICAM-3; CD50) and ICAM-2 (CD102) triggers transmigration of human immunodeficiency virus type 1-infected monocytes through mucosal epithelial cells. Journal of virology 30 11739669
1994 LFA-1 binding site in ICAM-3 contains a conserved motif and non-contiguous amino acids. Cell adhesion and communication 30 7531103
1993 ICAM-3 expression on endothelium in lymphoid malignancy. The American journal of pathology 30 8214000
2008 Cooperation of specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) and complement receptor type 3 (CR3) in the uptake of oligomannose-coated liposomes by macrophages. Glycobiology 29 19029201
1995 Epitope mapping and functional properties of anti-intercellular adhesion molecule-3 (CD50) monoclonal antibodies. European journal of immunology 29 7875209
1995 Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients. Journal of immunology (Baltimore, Md. : 1950) 29 7876564
2007 Association of ICAM3 genetic variant with severe acute respiratory syndrome. The Journal of infectious diseases 28 17570115
2006 DC-SIGN binds ICAM-3 isolated from peripheral human leukocytes through Lewis x residues. Glycobiology 28 17145745
1995 Heterogenous glycosylation of ICAM-3 and lack of interaction with Mac-1 and p150,95. European journal of immunology 27 7737271
2017 Increased Cell Adhesion Molecules, PECAM-1, ICAM-3, or VCAM-1, Predict Increased Risk for Flare in Patients With Quiescent Inflammatory Bowel Disease. Journal of clinical gastroenterology 26 27552332
1998 Coengagement of ICAM-3 and Fc receptors induces chemokine secretion and spreading by myeloid leukocytes. Journal of immunology (Baltimore, Md. : 1950) 24 9605163
1999 ICAM-3 and E-selectin endothelial cell expression differentiate two phases of angiogenesis in infantile hemangiomas. Journal of cutaneous pathology 23 10189240
1998 Induction of sensitivity to NK-mediated cytotoxicity by TNF-alpha treatment: possible role of ICAM-3 and CD44. Leukemia 23 9766501
2001 Structural study of N-linked oligosaccharides of human intercellular adhesion molecule-3 (CD50). European journal of biochemistry 22 11179968
2018 ICAM3 mediates tumor metastasis via a LFA-1-ICAM3-ERM dependent manner. Biochimica et biophysica acta. Molecular basis of disease 21 29729315
2008 Binding of the Streptococcus gordonii DL1 surface protein Hsa to the host cell membrane glycoproteins CD11b, CD43, and CD50. Infection and immunity 21 18678668
1997 Antibodies to the beta 1-integrin chain, CD44, or ICAM-3 stimulate adhesion of blast colony-forming cells and may inhibit their growth. Experimental hematology 21 9131010
2018 Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses. Frontiers in immunology 19 29662482
2000 Human leukemic (HMC-1) mast cells are responsive to 1alpha, 25-dihydroxyvitamin D(3): selective promotion of ICAM-3 expression and constitutive presence of vitamin D(3) receptor. Biochemical and biophysical research communications 19 10891379
1995 B-cell homotypic adhesion through exon-A restricted epitopes of CD45 involves LFA-1/ICAM-1, ICAM-3 interactions, and induces coclustering of CD45 and LFA-1. Blood 19 7544645
2004 ICAM-3 activation modulates cell-cell contacts of human bone marrow endothelial cells. Journal of vascular research 18 14726630
1994 The human intercellular adhesion molecule 3 (ICAM3) gene is located in the 19p13.2-p13.3 region, close to the ICAM1 gene. Genomics 18 7851905
1999 Regulation of ICAM-3 and other adhesion molecule expressions on eosinophils in vitro. Effects of dexamethasone. Allergy 17 10688433
2001 Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion--evidence for retinoid signaling pathways in the mast cell lineage. Journal of leukocyte biology 15 11261782
1998 Engagement of ICAM-3 activates polymorphonuclear leukocytes: aggregation without degranulation or beta 2 integrin recruitment. Journal of immunology (Baltimore, Md. : 1950) 15 9834117
1995 Intercellular adhesion molecule-3 (CD50) on human epidermal Langerhans cells participates in T-cell activation. The Journal of investigative dermatology 15 7539471
2000 CD4+ T cell and eosinophil adhesion is mediated by specific ICAM-3 ligation and results in eosinophil activation. Journal of immunology (Baltimore, Md. : 1950) 14 10706734
1998 Mapping of the ICAM-5 (telencephalin) gene, a neuronal member of the ICAM family, to a location between ICAM-1 and ICAM-3 on human chromosome 19p13.2. Genomics 14 9828136
1997 CD50 monoclonal antibodies inhibit neutrophil activation. Journal of immunology (Baltimore, Md. : 1950) 14 9218600
1996 Stimulation through CD50 (ICAM-3) induces both activation and programmed cell death of human thymocytes. Tissue antigens 14 9008304
1995 CD50 (intercellular adhesion molecule-3) is expressed at higher levels on memory than on naive human T cells but induces a similar calcium mobilization on both subsets. Tissue antigens 14 7482494
2013 ICAM-3 endows anticancer drug resistance against microtubule-damaging agents via activation of the ICAM-3-AKT/ERK-CREB-2 pathway and blockage of apoptosis. Biochemical and biophysical research communications 13 24177012
2011 The neuronal protein Kidins220/ARMS associates with ICAM-3 and other uropod components and regulates T-cell motility. European journal of immunology 13 21381019
2000 Soluble and cell surface ICAM-3 in blood and cerebrospinal fluid of patients with multiple sclerosis: influence of methylprednisolone treatment and relevance as markers for disease activity. Acta neurologica Scandinavica 13 10685862
1998 The leukocyte function-associated antigen-1 (LFA-1)-binding site on ICAM-3 comprises residues on both faces of the first immunoglobulin domain. Journal of immunology (Baltimore, Md. : 1950) 13 9686599
1992 Effect of protein kinase C activators on the phosphorylation and the surface expression of the CDw50 leukocyte antigen. European journal of biochemistry 13 1730238
2000 CD50 and CD62L adhesion receptor expression on naive (CD45RA+) and memory (CD45RO+) T lymphocytes in the elderly. Pathobiology : journal of immunopathology, molecular and cellular biology 12 11493756
2000 CD45RA+ ICAM-3+ lymphocytes in cerebrospinal fluid and blood as markers of disease activity in patients with multiple sclerosis. Acta neurologica Scandinavica 11 11083511
1999 ICAM-3 (CD50) cross-linking augments signaling in CD3-activated peripheral human T lymphocytes. Journal of leukocyte biology 10 10380912
1995 Expression of ICAM-3/CD50 in normal and diseased skin. The British journal of dermatology 10 8546991
1996 Expression of intercellular adhesion molecule-3 (ICAM-3/CD50) in malignant lymphoproliferative disorders and solid tumors. Tissue antigens 9 8946680
2019 ICAM3-Fc Outperforms Receptor-Specific Antibodies Targeted Nanoparticles to Dendritic Cells for Cross-Presentation. Molecules (Basel, Switzerland) 8 31083610
1995 Expression of ICAM-3 on human epidermal dendritic cells. Immunobiology 8 7782098
1993 Isolation and characterisation of a CDw50 negative Jurkat T-cell line variant (PPL.1). Leukemia research 8 8429685
2007 ICAM-3 influences human immunodeficiency virus type 1 replication in CD4(+) T cells independent of DC-SIGN-mediated transmission. Virology 7 17434553
1999 ICAM-3 (CD50) is expressed by human mast cells: induction of homotypic mast cell aggregation via ICAM-3. Cell adhesion and communication 7 10626904
1998 Stimulation through CD50 preferentially induces apoptosis of TCR1+ human peripheral blood lymphocytes. Cell adhesion and communication 7 9929740
2007 An intercellular adhesion molecule-3 (ICAM-3) -grabbing nonintegrin (DC-SIGN) efficiently blocks HIV viral budding. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 17962491
2005 ICAM-3, a ligand for DC-SIGN, was duplicated from ICAM-1 in mammalian evolution, but was lost in the rodent genome. FEBS letters 6 15890347
1995 Expression of the intercellular adhesion molecule-3 (ICAM-3) in human renal tissue with relation to kidney transplants and various inflammatory diseases. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 6 7576578