Regulation by fibrinogen and its products of intercellular adhesion molecule-1 expression in human saphenous vein endothelial cells

It has been reported that fibrinogen may act as a bridging ligand, binding to intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells and to Mac-1 on THP-1 cells (a monocytic cell line) to increase adhesion. In this study, we investigated whether fibrinogen altered the expression of ICAM-1 and, thus, increased the adhesion of THP-1 cells to cultured human saphenous vein endothelial cells (HSVECs). Incubation of: HSVECs with 0.3 to 4 mu mol/L fibrinogen caused a time- and concentration-dependent increase in ICAM-1, as determined by ELISA. The 4- to 5-fold increase in ICAM-1 protein concentration in HSVECs stimulated by 4 mu mol/L fibrinogen for 6 hours was concomitant with a 4- to 5-fold increase in ICAM-1 mRNA. This fibrinogen-stimulated ICAM-1 upregulation was associated with a 2-fold increase in THP-1 cell adhesion to HSVECs, The fibrinogen-derived peptide B beta 15-42 bound to HSVECs (K-d 0.18 mu mol/L). Preincubation of HSVECs with Bp15-42, a neutralizing antibody to urokinase plasminogen activator (uPA), or the F(ab)(1) fragment of a monoclonal antibody to vascular endothelial cadherin significantly attenuated the increase in ICAM-1 stimulated by fibrinogen, Capillary electrophoretic analysis indicated that anti-uPA prevented the release of any fibrinopeptide B (B beta 1-14) in cultures of HSVECs incubated with 4 mu mol/L fibrinogen for 6 hours, Moreover, incubation of HSVECs with either fibrin monomer (1 mu mol/L) or monoclonal antibodies to vascular endothelial cadherin (25 mu g/mL) increased ICAM-1 protein concentration 3- to 4-fold. These findings indicate that cleavage of fibrinopeptide B from fibrinogen by endothelial uPA permits the exposed B beta 15-42 sequence of fibrinogen to bind to vascular endothelial cadherin on HSVECs and to upregulate the expression of ICAM-1.