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Intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig superfamily, contains five Ig-like domains comprising the extracellular portion of the molecule, and interacts with lymphocyte function-associated molecule-1 (LFA-1), a member of the beta 2-integrin family. LFA-1/ICAM-1 interaction is important in a variety of cellular events including Ag-specific T cell activation and leukocyte transendothelial migration. Recently, a soluble circulating form of ICAM-1 has been detected in human serum that appears to result from the proteolytic cleavage of membrane ICAM-1. Native and recombinant soluble forms of ICAM-1 have been reported to inhibit LFA-1/ICAM-mediated adhesion in vitro, and it is conceivable that circulating forms of soluble ICAM-1 are regulators of LFA-1/ICAM-1-mediated cell-cell interaction in vivo. We have investigated the properties of the ICAM-1 ectodomain (sICAM453) as an inhibitor of LFA-1 interaction with ICAM-1 in cell- and molecule-based systems. The results show clearly that recombinant sICAM453 can inhibit LFA-1/ICAM-1 interaction. Soluble ICAM-1 inhibited LFA-1-mediated cell adhesion to immobilized sICAM453 and homotypic T-cell aggregation with IC50 in the 20 to 40 microM range. Definitive evidence that sICAM-1 can inhibit LFA-1 interaction with ICAM-1 was obtained by showing that the sICAM-1 inhibited the interaction between LFA-1 protein micelles and ICAM-1 immobilized on plastic. These results clearly show that sICAM453 can bind to LFA-1 and competitively inhibit ICAM-1/LFA-1-mediated cell-cell interaction, albeit at concentrations much greater than found in plasma. As a consequence, it is unlikely that sICAM-1 would antagonize ICAM-1/LFA-1-mediated cellular events in vivo.

Type

Journal article

Journal

J Immunol

Publication Date

01/10/1995

Volume

155

Pages

3578 - 3584

Keywords

Animals, Cell Adhesion, Cell Aggregation, Cell Communication, Humans, Intercellular Adhesion Molecule-1, Lymphocyte Function-Associated Antigen-1, T-Lymphocytes