Intercellular adhesion molecule-1

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-alpha, interleukin-1, and interferon-gamma, 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 kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, 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 sICAM-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.

Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1, CD54) in patients with non-small-cell lung cancer: correlation with histological expression of ICAM-1 and tumour stage

“…British Journal of Cancer (1998) 77(5) Saag, 1996), and also in non-malignant acute (infectious) and chronic diseases, such as acute infectious mononucleosis (Furukawa et al, 1993), P. falciparum malaria (Hvidd et al, 1993), autoimmune and viral hepatitis (Zohrens et al, 1993), alcoholic liver cirrhosis (Zohrens et al, 1993), extrinsic allergic alveolitis (Shijubo et al, 1995), acute attacks of bronchial asthma (Kobayashi et al, 1994), inflammatory bowel disease (Patel et al, 1995), systemic lupus erythematosus (Mrowka and Sieberth, 1994), active multiple sclerosis (Sharief et al, 1993;Tsukada et al, 1993;Rieckmann et al, 1995), diabetes (Roep et al, 1994) and chronic renal failure .…”

“…The molecule might represent the extracellular part of the membrane-bound ICAM-1 split off by proteolytic cleavage and shed into the extracellular fluid (van de Stolpe and van der Saag, 1996). Alternatively, sICAM-1 could be produced as a secreted splice variant of ICAM-l lacking the intramembrane and intracellular domains, however no corresponding spliced mRNA has yet been identified (Budnik et al, 1996).…”

“…IFN-y, TNF-a) and also by lipopolysaccharid (LPS), oxygen radicals and hypoxia. It is then present in white blood cells, fibroblasts, endothelial cells and some epithelial tissues (van de Stolpe and van der Saag, 1996). The ICAM-1-mediated contact between leucocytes and endothelial cells is a mandatory step in the interaction of these two cell systems, i.e.…”

Inhibition of Lipopolysaccharide Activity by a Bacterial Cyclic Lipopeptide Surfactin

“…The most important of the adhesion molecules involved in this process are intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin [8,9]. Without stimulation, only a small amount of ICAM-1 is present on the endothelial cell surface [10], and VCAM-1 and E-selectin are absent entirely [11,12], but they are immediately expressed in response to extracellular inflammatory stimulation [13]. ICAM-1 interacts with the ligand CD11a/CD18 (LFA-1), which is expressed on neutrophils, lymphocytes, and monocytes; and VCAM-1, with the ligand VLA-4, which is expressed on lymphocytes.…”

Inhibition of the α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat cells

“…van de Stolpe and van der Saag reviewed the factors regulating the expression of CD54 gene reported in the literature. They included the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors and post-transcriptional modification [24]. MAN2C1 deficiency caused by the inhibition of Man2c1 gene expression might affect N-glycosylation of proteins including CD54 and CD11a, consequently influencing their expression.…”