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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:652.)
© 2000 American Heart Association, Inc.

Vascular Biology

Regulation by Fibrinogen and Its Products of Intercellular Adhesion Molecule-1 Expression in Human Saphenous Vein Endothelial Cells

Suzanne L. Harley; Justin Sturge; Janet T. Powell

From the Department of Vascular Surgery, Imperial School of Medicine at Charing Cross Hospital, London, UK.

Correspondence to Prof Janet T. Powell, Department of Vascular Surgery, Imperial School of Medicine at Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK. E-mail j.powell{at}ic.ac.uk

Abstract—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 µmol/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 µmol/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 Bß15-42 bound to HSVECs (K_d 0.18 µmol/L). Preincubation of HSVECs with Bß15-42, 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 (Bß1-14) in cultures of HSVECs incubated with 4 µmol/L fibrinogen for 6 hours. Moreover, incubation of HSVECs with either fibrin monomer (1 µmol/L) or monoclonal antibodies to vascular endothelial cadherin (25 µg/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 Bß15-42 sequence of fibrinogen to bind to vascular endothelial cadherin on HSVECs and to upregulate the expression of ICAM-1.

Key Words: fibrinogen • intercellular adhesion molecule-1 • saphenous vein endothelium • vascular endothelial cadherin • Bß15–42

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