Augmentation of procoagulant activity in monokine stimulated human endothelial cells by calmodulin/protein kinase C inhibitors.
The incubation of human umbilical cord endothelial cell cultures with inflammatory mediators results in the induction of procoagulant activity. As many of these mediators activate protein kinase C, the effect of calmodulin and protein kinase C inhibitors on IL-1, TNF, phorbol ester and LPS stimulated procoagulant activity was determined. Incubation of endothelial cell cultures with these inflammatory agents in the presence of phenothiazine derivatives or other classes of calmodulin and protein kinase C antagonists resulted in a 2-4 fold increase in procoagulant activity compared to parallel stimulated cultures in the absence of antagonists. The augmented response of IL-1 stimulated endothelial cells to these antagonists was actinomycin D sensitive.
Zuckerman
S H
SH
Department of Immunology, Lilly Research Labs, Indianapolis, IN 46285.
Surprenant
Y M
YM
D001688:Biological Products / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015846:Monokines; D010640:Phenothiazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013268:Stimulation, Chemical
D001688:Biological Products; D001779:Blood Coagulation Factors; D002147:Calmodulin; D015846:Monokines; D010640:Phenothiazines; D011493:Protein Kinase C