Release of a leukocyte activation inhibitor by staurosporine-treated pulmonary artery endothelial cells.
Bovine pulmonary arterial endothelial cells (BPAE) treated with the protein kinase C (PKC) inhibitor staurosporine inhibited O-2. generation by neutrophils exposed to phorbol myristate acetate (PMA) but did not affect O-2. generated enzymatically by xanthine/xanthine oxidase (X/XO). Similar results were obtained with conditioned medium from staurosporine-pretreated BPAE. The inhibitory effects of staurosporine-treated BPAE on O-2. generation were not altered by the superoxide dismutase inhibitor diethylcarbamazine. This BPAE-derived inhibitor was continuously released from staurosporine-pretreated BPAE for at least 5 h. The exact nature of the inhibitor remains unknown, but it appears to be a positively charged molecule with molecular weight <10,000. Treatment of either BPAE or neutrophils with staurosporine or conditioned medium from staurosporine-treated BPAE prevented the neutrophil-mediated decrease in endothelium-bound angiotensin-converting enzyme activity and cytotoxicity in BPAE. In contrast, staurosporine potentiated the H2O2- and X/XO-mediated endothelial cytotoxicity. These data suggest that staurosporine-treated endothelial cells release a soluble factor that inhibits neutrophil activation and protects endothelial cells from neutrophil-mediated injury.
Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA.
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Catravas
D000818:Animals; D001685:Biological Factors / Q000378:metabolism* / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004049:Diethylcarbamazine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery; D011817:Rabbits; D019311:Staurosporine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001685:Biological Factors; D017077:Culture Media, Conditioned; D013481:Superoxides; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D007703:Peptidyl-Dipeptidase A; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D004049:Diethylcarbamazine