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.
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1 October 1985
Article|
October 01 1985
Self-regulation of procoagulant events on the endothelial cell surface.
D M Stern
I Bank
P P Nawroth
J Cassimeris
W Kisiel
J W Fenton, 2nd
C Dinarello
L Chess
E A Jaffe
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1985) 162 (4): 1223–1235.
Citation
D M Stern, I Bank, P P Nawroth, J Cassimeris, W Kisiel, J W Fenton, C Dinarello, L Chess, E A Jaffe; Self-regulation of procoagulant events on the endothelial cell surface.. J Exp Med 1 October 1985; 162 (4): 1223–1235. doi: https://doi.org/10.1084/jem.162.4.1223
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