THROMBIN-ACTIVATED HUMAN ENDOTHELIAL-CELLS SUPPORT MONOCYTE ADHESION IN-VITRO FOLLOWING EXPRESSION OF INTERCELLULAR-ADHESION-MOLECULE-1 (ICAM-1, CD54) AND VASCULAR-CELL-ADHESION-MOLECULE-1 (VCAM-1, CD106)

Thrombin, a central molecule in coagulation, is also involved in infla mmation. Notably, thrombin induces endothelial neutrophil adhesion, P- and E-selectin expression, and chemokine production. We show here tha t thrombin induces expression of intercellular adhesion molecule-1 (IC AM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106) on h uman umbilical vein endothelial cells (HUVECs) associated with increas ed adhesion of monocytes. Thrombin increased mRNA steady-state levels and expression of ICAM-1 over 24 hours. Thrombin-induced VCAM-1 expres sion exhibited unusual kinetics, reaching maximum levels after 6 to 12 hours, but decreasing to near baseline after 24 hours. Thrombin activ ity on HUVECs was mediated through interaction with its specific recep tor, because ICAM-1 and VCAM-1 expression were similarly induced by th e 14-amino acid thrombin receptor-activating peptide, Thrombin-induced ICAM-1 and VCAM-1 expression was significantly inhibited by hirudin, but not by interleukin-1 receptor antagonist or anti-tumor necrosis fa ctor alpha monoclonal antibody (MoAb), Thrombin-activated HUVECs signi ficantly increased greater numbers of adhering THP-1 macrophagic cells , peripheral blood mononuclear cells, or purified monocytes than unsti mulated HUVECs. This adhesion was inhibited by anti-CD18 and anti-CD49 d MoAb, demonstrating that thrombin-induced ICAM-1 and VCAM-1 were fun ctional. These results show that, in addition to selectins, thrombin d irectly induces a cytokine-independent expression of adhesion molecule s of the Ig superfamily on HUVECs that may support firm leukocyte atta chment during inflammation. (C) 1998 by The American Society of Hemato logy.