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Intercellular adhesion molecule-1

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Abstract

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-α, interleukin-1, and interferon-γ, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel κB element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-α, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of s-lCAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.

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Abbreviations

ICAM :

Intercellular adhesion molecule

IFN :

Interferon

IL :

Interleukin

LFA :

Leukocyte function associated antigen

mAb :

Monoclonal antibody

mICAM-1 :

Membrane-bound ICAM-1

NF :

Nuclear factor

NHL :

Non-Hodgkin lymphoma

RAR :

Retinoic acid receptor

sICAM-1 :

Soluble ICAM-1

TNF :

Tumor necrosis factor

TPA :

12-O-Tetradecanoylphorbol-13-acetate

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  1. Department of Hematology, University Hospital Nijmegen, Postbus 9101, 6500, HB Nijmegen, The Netherlands

    A. van de Stolpe

  2. Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Utrecht, The Netherlands

    P. T. van der Saag

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van de Stolpe, A., van der Saag, P.T. Intercellular adhesion molecule-1. J Mol Med 74, 13–33 (1996). https://doi.org/10.1007/BF00202069

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