Endothelium from diverse vascular sources synthesizes platelet-activating factor.
Stimulation of cultured bovine endothelial cells from aorta, pulmonary artery, coronary artery, and vena cava with calcium ionophore A23187, adenosine triphosphate (ATP), bradykinin, and angiotensin II resulted in production of platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine. In pulmonary artery endothelial cells, maximal accumulation occurred within 20 minutes, and the PAF remained cell-associated. This response was concentration-dependent with a maximal effect at 10(-8)M bradykinin and 10(-6)M angiotensin II. Stimulation of in situ endothelial cells on isolated strips of bovine pulmonary artery with calcium ionophore, ATP, and bradykinin also resulted in production of PAF. In cultured pulmonary artery endothelial cells, PAF appeared only in response to the same agonists that caused prostacyclin (PGI2) release. These findings are similar to earlier studies with human umbilical vein endothelial cells and suggest that the production of PAF and the arachidonate metabolite PGI2 are tightly linked in these vessels. Aortic endothelial cells, both in culture and on isolated strips of aorta, also produced PAF in response to bradykinin in a time-and concentration-dependent fashion. Cultured endothelial cells from coronary vessels and the inferior vena cava accumulated PAF when appropriately stimulated as well. The finding that both cultured endothelial cells and in situ, ex vivo endothelium from diverse vascular sites produce PAF when appropriately stimulated suggests that this is a generalized response of endothelial cells. Because PAF has potent vasoactive, pro-aggregatory, and pro-inflammatory effects, the results from these experiments suggest that the local accumulation of this lipid may be important in vascular injury and inflammation.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008722:Methods; D010972:Platelet Activating Factor / Q000032:analysis / Q000096:biosynthesis*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D014682:Vena Cava, Inferior / Q000187:drug effects / Q000378:metabolism
D010972:Platelet Activating Factor; D000804:Angiotensin II; D000001:Calcimycin; D000255:Adenosine Triphosphate; D001920:Bradykinin