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

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

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 Bβ15-42 bound to HSVECs (K(d) 0.18 μmol/L). Preincubation of HSVECs with Bβ15-42, 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 (Bβ1-14) 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 Bβ15-42 sequence of fibrinogen to bind to vascular endothelial cadherin on HSVECs and to upregulate the expression of ICAM-1.

Citation

Harley, S. L., Sturge, J., & Powell, J. T. (2000). Regulation by fibrinogen and its products of intercellular adhesion molecule-1 expression in human saphenous vein endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(3), 652-658. https://doi.org/10.1161/01.ATV.20.3.652

• Journal Article Type: Article
• Acceptance Date: Sep 7, 1999
• Online Publication Date: Mar 1, 2000
• Publication Date: 2000-03
• Deposit Date: Jun 27, 2019
• Journal: Arteriosclerosis, Thrombosis, and Vascular Biology
• Print ISSN: 1079-5642
• Electronic ISSN: 1524-4636
• Publisher: American Heart Association
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 3
• Pages: 652-658
• DOI: https://doi.org/10.1161/01.ATV.20.3.652
• Keywords: Cardiology and Cardiovascular Medicine
• Public URL: https://hull-repository.worktribe.com/output/2015643
• Publisher URL: https://www.ahajournals.org/doi/10.1161/01.ATV.20.3.652