REGULATION OF LEUKOCYTE-ENDOTHELIUM INTERACTION AND LEUKOCYTE TRANSENDOTHELIAL MIGRATION BY INTERCELLULAR-ADHESION MOLECULE 1-FIBRINOGEN RECOGNITION

Although primarily recognized for its role in hemostasis, fibrinogen i s also required for competent inflammatory reactions in vivo, It is no w shown that fibrinogen promotes adhesion to and migration across an e ndothelial monolayer of terminally differentiated myelomonocytic cells , This process does not require chemotactic/haptotactic gradients or c ytokine stimulation of the endothelium and is specific for the associa tion of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium, Among other adhesive plasma proteins, fibronectin fails t o increase the binding of leukocytes to endothelium, or transendotheli al migration, whereas vitronectin promotes the binding but not the mig ration, The fibrinogen-mediated leukocyte adhesion and transendothelia l migration could be inhibited by a peptide from the fibrinogen gamma- chain sequence N(117)NQKIVNLKEKVAQLEA(133), which blocks the binding o f fibrinogen to ICAM-1. This interaction could also be inhibited by ne w anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD1 1a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implica ted in leukocyte-endothelium interaction, Therefore, binding of fibrin ogen to vascular cell receptors is sufficient to initiate (i) increase d leukocyte adhesion to endothelium and (ii) leukocyte transendothelia l migration, These two processes are the earliest events of immune inf lammatory responses and may also contribute to atherosclerosis.