Self-regulation of procoagulant events on the endothelial cell surface.
Interleukin 1 (IL-1) is a potent mediator of inflammatory and immunologic phenomena. In addition, IL-1 may be intimately involved in the regulation of hemostasis, since interaction of IL-1 with endothelial cells has been reported to induce tissue factor activity. We demonstrate that perturbation of the endothelial cell induces augmented IL-1 release. Human umbilical vein endothelial cells perturbed by treatment with lipopolysaccharide produced enhanced amounts of IL-1 activity. IL-1 activity from lipopolysaccharide-treated endothelial cell supernatants could be absorbed by an antibody to IL-1 coupled to Sepharose. Elaboration of IL-1 activity was dependent on the dose of lipopolysaccharide and occurred in a time-dependent manner. Addition of cycloheximide blocked generation of IL-1 activity. A physiological vessel wall perturbant, the coagulation enzyme thrombin, induced comparable amounts of IL-1 activity in endothelial cell cultures. This effect was specific for the enzyme, since active site-blocked thrombin and prothrombin had no effect on IL-1. In addition, IL-1-containing supernatants from thrombin-stimulated endothelial cells induced tissue factor procoagulant activity in fresh endothelial cell cultures. Thus, in contrast to the multiple, known inhibitory mechanisms that block thrombin procoagulant activity, these data suggest a circle of interaction in which thrombin induces endothelial cell elaboration of IL-1, a mediator of endothelial cell procoagulant activity. Endothelial cell production of IL-1 in response to perturbation allows these cells to play an integral role in the regulation of the inflammatory and coagulation systems.
D000818:Animals; D001777:Blood Coagulation; D002478:Cells, Cultured; D004727:Endothelium / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins / Q000378:metabolism
D007375:Interleukin-1; D008070:Lipopolysaccharides; D013917:Thrombin