IDENTIFICATION OF AN ACTIVE SEQUENCE WITHIN THE FIRST IMMUNOGLOBULIN DOMAIN OF INTERCELLULAR CELL-ADHESION MOLECULE-1 (ICAM-1) THAT INTERACTS WITH FIBRINOGEN

Monocytic cells bind fibrinogen (fg) through integrin alpha(M) beta(2) . fg-bound monocytic cells demonstrate an enhanced adhesion to endothe lial cells, which is dependent on intercellular adhesion molecule-1 (I CAM-1). Our studies differentiate fg interactions with stimulated and resting endothelial cells, which are ICAM-1 dependent and independent, respectively. This report documents a direct interaction between fg a nd intact ICAM-1 and with a two-Ig domain form of ICAM-1. A small regi on within the first Ig domain of ICAM-1, ICAM-1-(8-21) (KVILPRGGSVLVTC ), was identified to interact with fg in a specific and selective mann er. ICAM-1-(8-21) bound to plasmin-derived fg fragments X, D100, and D 80 but not to fragment E. Consistent with this finding, fg gamma-chain peptide, fg-gamma-117-133, blocked fg interaction with ICAM-1-(8-21). ICAM-1-(8-21) peptide and antibodies directed against ICAM-1-(8-21) a lso blocked the adhesion and binding of ICAM-1-bearing Raji cells with fg. ICAM-1-(8-21) and fg-gamma-117-133 are likely to be one of the co ntact pairs mediating fg-ICAM-1 interactions.