Prostaglandin and thromboxane production by fibroblasts and vascular endothelial cells.
We have compared the production of prostaglandins in fibroblast-like cells and endothelial cells in culture. Of the fibroblasts studied 10T1/2, SHE, BP6T and KD produce significant amounts of PGI2, PGE2 and PGF2F2 under optimal culture conditions, but only 3T3 and BHK produce TXA2 in addition to PGI2. The adult bovine aortic endothelial cells (ABAE) and fetal bovine heart endothelium (FBHE) synthesise PGI2 but not TXA2, either from endogenous or exogenous substrates. Both cultured endothelial cells and fibroblasts apparently lack 15-hydroxyprostaglandin dehydrogenase pathway and the ability to convert 6-Keto PGF1 alpha into 6-Keto PGE1. PGI2 production by ABAE was 3-5 times that of FBHE, about twice that of SHE cells and 6-8 times that of 10T1/2 or BP6T cells. Supernatants or media obtained from these cells inhibited aggregation of human platelet-rich plasma, a known biological effect of PGI2. This effect was abolished when cell monolayers were preincubated with indomethacin or tranylcypromine. RIA and chromatographic data of 6-Keto PGF1 alpha from these experiments confirmed that the inhibition of platelet aggregation was due to the formation of PGI2. The production of all prostanoids by endothelial cells or fibroflasts was significantly higher during the exponential phase of growth as compared to confluent monolayers. We propose that fibroblasts 10T1/2 or SHE can serve as useful experimental models for the study of metabolism and transport of PGI2 and/or TXA2 in cells of nonendothelial nature.
D000818:Animals; D001011:Aorta / Q000166:cytology*; D002417:Cattle; D002478:Cells, Cultured; D006224:Cricetinae; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006321:Heart / Q000196:embryology; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D009206:Myocardium / Q000166:cytology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; D011464:Epoprostenol