Procoagulant Human Monocytes Mediate Tissue Factor/Factor VIIa–Dependent Platelet-Thrombus Formation When Exposed to Flowing Nonanticoagulated Human Blood

Autor: Åse-Brit Westvik, M. J. A. G. Hamers, Kjell S. Sakariassen, P. Kierulf, R. M. Barstad
Rok vydání: 1995
Předmět:
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 15:11-16
ISSN: 1524-4636
1079-5642
Popis: Abstract Tissue factor (TF) on monocyte and macrophage surfaces is a nonproteolytic cofactor for factor VIIa (FVIIa)–induced coagulation. Monocyte-derived macrophages in atherosclerotic plaques express TF, which, after plaque disruption or rupture, may complex with FVII/VIIa from the bloodstream, resulting in activation of extrinsic coagulation. We studied the effect of TF expression on human monocytes on arterial thrombus formation in a model system of thrombogenesis. Thawed, cryopreserved human monocytes adherent to plastic coverslips were stimulated with lipopolysaccharide (0.5 μg/mL) to express TF and subsequently exposed to flowing nonanticoagulated human blood in a parallel-plate perfusion chamber. The wall shear rate at the cell surface was 650 seconds −1 , corresponding to that of average-sized coronary arteries. The stimulated monocytes elicited pronounced fibrin deposition and platelet-thrombus formation. The platelet-thrombus volume was as large as that triggered by human type III collagen fibrils under similar experimental conditions. In contrast, the monocytes elicited much more fibrin deposition than the collagen surface. However, inclusion of an anti-TF monoclonal antibody that blocks the complexation of FVII/FVIIa with TF virtually abolished the fibrin deposition ( P P
Databáze: OpenAIRE