Characterization of platelet-activating factor synthesis in glomerular endothelial cell lines.
Platelet-activating factor synthesis in two transformed lines of glomerular endothelial cells was characterized and contrasted with platelet-activating factor production in macrovascular-derived endothelial cells as well as with glomerular cells of mesenchymal origin. Platelet-activating factor synthesis was assessed in intact cells and in cell-free preparations. Glomerular endothelial cells constitutively synthesize bio-active alkyl-PAF, and this basal activity can be chronically augmented by various inflammatory and thrombotic agents. In contrast, thrombin-mediated platelet-activating factor formation in bovine pulmonary aortic endothelial cells as well as in glomerular mesangial cells is acute and transient. The potential role of anti-inflammatory prostanoids to function as negative feedback modulators of thrombin- or endothelin-mediated platelet-activating factor synthesis was also investigated, as the synthesis of platelet-activating factor is often associated with the formation of these prostanoids. Indomethacin augmented receptor-mediated platelet-activating factor synthesis while prostanoids of the E and I series reduced agonist-stimulated PAF synthesis. In summary, the unique capacity of glomerular endothelial cells to respond to inflammatory stimuli with sustained platelet-activating factor synthesis is a clear indication of this cell's pivotal role in augmenting the inflammatory response in the limited environment of the glomerulus.
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
M
M
Kester
R J
RJ
Nowinski
H
H
Holthöfer
P A
PA
Marsden
M J
MJ
Dunn
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000098:blood supply / Q000166:cytology / Q000201:enzymology; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000166:cytology / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology
D016232:Endothelins; D010972:Platelet Activating Factor; D011453:Prostaglandins; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D013917:Thrombin; D007213:Indomethacin