Disease relevance of ICAM3

• It is able to bind ICAM3 and HIV gp120 in a calcium-dependent manner [1].
• Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses [2].
• In all three types of immune disorders, lymphocytes expressed the integrins alpha4/beta1 (VLA4) and ICAM3, whereas lymphocytes in COPD bronchitis and in emphysema controls were unreactive [3].
• A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection [4].
• In 52 cases of Hodgkin's disease, ICAM-3, although present on the majority of the reactive lymphoid cells, was absent from the Reed-Sternberg cells and their variants [5].

High impact information on ICAM3

• Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses [6].
• Here, we demonstrate that ICAM-3 expressed by resting T cells is important in this first contact with DC [6].
• ICAM-3 is closely related to ICAM-1, consists of five immunoglobulin domains, and binds LFA-1 through its two N-terminal domains [7].
• Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11, 12) [7].
• The high level of expression of ICAM-R on resting leukocytes of all lineages and its lack of expression on either resting or cytokine-activated endothelial cells indicates a pattern of expression distinct from ICAM-1 and ICAM-2 [8].

Chemical compound and disease context of ICAM3

• DC-SIGN binds to HIV-1 glycoprotein 120 in a distinct but overlapping fashion compared with ICAM-2 and ICAM-3 [9].
• Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients [10].
• 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 [11].

Biological context of ICAM3

• The complementary DNA encoding ICAM-R is 1,781 base pairs long and the protein has five extracellular immunoglobulin-family type domains [8].
• Altogether, these data indicate that moesin interacts with ICAM-3 and CD44 adhesion molecules in uropods of polarized T cells; these data also suggest that these interactions participate in the formation of links between membrane receptors and the cytoskeleton, thereby regulating morphological changes during cell locomotion [12].
• Analysis of a panel of 45 point mutants of domain 1 of ICAM-3 identified five residues that may contact LFA-1 as part of the binding site, Asn23, Ser25, Glu37, Phe54, and Gln75 [13].
• In addition to an adhesive function, ICAM-3 can act as a signal-transducing molecule on T cells, providing a costimulatory signal for cell proliferation [14].
• Intense expression of ICAM-R by rheumatoid synovial lymphocytes and macrophages suggests that it may play a role in processes requiring cell-cell contact, such as antigen presentation and homotypic aggregation [15].

Anatomical context of ICAM3

• Expression of VLA4 and ICAM3 on lymphocytes, however, might be a specific event in all three immune reactions [3].
• Eosinophils in atopic asthma bronchitis in contrast to COPD bronchitis also expressed both VLA4 and ICAM3 [3].
• A synthetic peptide containing the Ile-Lys-Gly-Asn motif inhibited ICAM-3-dependent adhesion and proliferation of T cells at micromolar concentrations, suggesting that this peptide interferes with immune recognition [16].
• ICAM-3 expression on endothelium in lymphoid malignancy [5].
• In the present study, we show immunocytochemically that ICAM-3 is present on T and B cells in the mantle zones and on a subpopulation of follicular center cells in reactive lymph nodes and only occasionally in endothelium [5].

Associations of ICAM3 with chemical compounds

• Other leukointegrin ligands therefore probably exist, such as a glycoprotein of M(r) 124K that binds LFA-1 and has been designated ICAM-3 on the basis of this function [8].
• Using a panel of human/murine I domain chimeras and point mutants, we observed that the Ile-Lys-Gly-Asn motif, located in the NH2-terminal part of the CD11a I domain, is required for ICAM-3 but not ICAM-1 binding [16].
• Thus, ICAM-3 was almost exclusively concentrated in the most distal portion of the heading uropod whereas either LFA-1 or the VLA beta 1 integrin were uniformly distributed all over the large contact area [17].
• Only SB 203580 could reverse the effect on CD11b, CD18, and ICAM-3 expressions [18].
• In addition, inhibitors of tyrosine kinase activity also abolished ICAM-3 and LFA-1-mediated cell aggregation [19].
• Patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P=.0067; odds ratio [OR], 4.31 [95% confidence interval {CI}, 1.37-13.56]) and lower total white blood cell counts (P=.022; OR, 0.30 [95% CI, 0.10-0.89]) on admission [20].

Physical interactions of ICAM3

• Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization [12].
• DC-SIGNR is expressed by restricted subsets of endothelial cells, but has similar ICAM-3 and HIV-binding properties to DC-SIGN [21].
• An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin alphaLbeta2 [22].
• Although all six Fabs internalized, three Fabs that showed the most complete blocking of HIVgp120 and ICAM-3 binding to L-SIGN also internalized most efficiently [23].
• ICAM-3 interacts with LFA1, and is involved in the intercellular adhesion of leukocytes as well as in the mainenance of cell survival [24].

Co-localisations of ICAM3

• The adhesion molecules PSGL-1 and ICAM-3 were found to colocalize with the cytoskeletal protein moesin in the uropod of stimulated neutrophils [25].

Regulatory relationships of ICAM3

• Homotypic thymocyte adhesion, however, is not decreased by CD54 mAb (anti-ICAM-1) but is inhibited by CDw50 mAb (anti-ICAM-3) [26].
• After 48-72-h culture in the presence of granulocyte/macrophage colony-stimulating factor, LC did not stain for ICAM-2 but expressed ICAM-3 at the same level as fresh cells [27].
• These data indicate that ICAM-3 is constitutively expressed by Langerhans cells and is a major ligand for LFA-1 on CD4+ T cells during their response to Langerhans cells [28].
• ICAM-3 regulates lymphocyte morphology and integrin-mediated T cell interaction with endothelial cell and extracellular matrix ligands [17].
• The results indicate that ICAM-3 is constitutively expressed and represents an important costimulatory molecule on freshly isolated LC but, in contrast to other accessory molecules, is not subjected to regulation during LC culture [27].

Other interactions of ICAM3

• The alpha d/CD18 molecule exhibits preferential recognition of ICAM-3 over ICAM-1 [29].
• Chemokines and other chemotactic cytokines induce lymphocyte polarization with the formation of a uropod in the rear pole, where the adhesion receptors intercellular adhesion molecule-1 (ICAM-1), ICAM-3, and CD44 redistribute [12].
• A correlation between the degree of moesin-ICAM-3 interaction and cell polarization was found as determined by immunofluorescence and immunoprecipitation analysis done in parallel [12].
• Dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209), a C-type surface lectin in human DCs, is a receptor for Leishmania amastigotes [30].
• Although ICAM-R is a ligand for LFA-1 and shares considerable sequence homology with ICAM-1 and ICAM-2, it does not appear to be expressed by the endothelium of normal or inflamed synovial vessels [15].

Analytical, diagnostic and therapeutic context of ICAM3

• Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes [7].
• Using a sandwich ELISA with two monoclonal anti-ICAM-3 Abs, we detected cICAM-3 in concentrations between 40 and 360 ng/ml in all of 112 healthy controls [31].
• ICAM-3 is a signal transducer and may play a key role in initiating immune responses [32].
• Ligation of intercellular adhesion molecule 3 induces apoptosis of human blood eosinophils and neutrophils [33].
• Immunohistochemistry of skin sections and flow-cytometry analysis of freshly procured epidermal cell suspensions showed that LC (CD1a+ or HLA-DR+) expressed ICAM-3 but not ICAM-2 [27].

References