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Relationship between tissue factor expression and deposition of fibrin,
platelets, and leukocytes on cultured endothelial cells under venous blood
flow conditions
D Kirchhofer, KS Sakariassen, M Clozel, TB Tschopp, P Hadvary, Y Nemerson and HR Baumgartner
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Endothelial cell-mediated coagulation and leukocyte adhesion are processes
that might be connected by the generation of thrombin. To examine the
interaction of procoagulant and proadhesive activity, cultures of
endothelial cells were stimulated with tumor necrosis factor-alpha, which
resulted in the surface expression of tissue factor. Subsequent exposure to
human nonanticoagulated blood at a shear rate of 100 s-1 in a parallel
plate perfusion device led to the deposition of polymerized fibrin, which
covered 63% of the endothelial surface. In addition, numerous platelet
aggregates (71 per 10 mm cross- section) and leukocytes (53 +/- 6/mm2) were
deposited on stimulated endothelial cells, whereas no fibrin and only a few
platelet aggregates (4 +/- 1 per 10 mm cross-section) and leukocytes (6 +/-
1/mm2) were detected on control cells. A significant portion of the
adherent leukocytes bound to fibrin and platelets. However, when the
deposition of fibrin and platelet aggregates was inhibited with the
anti-tissue factor antibody HTFI-7B8 by 100% and 86%, respectively,
leukocyte adherence remained unchanged (68 +/- 6/mm2). This indicated that
leukocytes could efficiently adhere to endothelial cells through direct
cell-cell contact independent of both thrombin and deposited fibrin.
Moreover, this direct adhesion of leukocytes to the endothelial surface was
reduced twofold to threefold when fibrin deposition occurred. These data
suggest a relationship between endothelial procoagulant and proadhesive
properties in that tissue factor-initiated coagulation may contribute to
leukocyte adhesion through the formation of an adhesive fibrin/platelet
meshwork but concurrently prevents the adhesive endothelial surface to bind
leukocytes at its full capacity.
Volume 81,
Issue 8,
pp. 2050-2058,
04/15/1993
Copyright © 1993 by The American Society of Hematology
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