Characterization of intercellular adhesion molecule-1 ectodomain (sICAM-1) as an inhibitor of lymphocyte function-associated molecule-1 interaction with ICAM-1.
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.
Meyer
D M
DM
Department of Immunology, Monsanto Company, St. Louis, MO 63198, USA.
Dustin
M L
ML
Carron
C P
CP
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1