title: Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2 in bladder microvascular endothelial cells.
abstract: Increased mast cell numbers and mast cell activation represent one of the prevalent etiologic theories for interstitial cystitis, an inflammatory condition in the bladder. This study was designed primarily to determine whether increased mast cell tryptase in the bladder wall may play a role in activating bladder endothelial cell phospholipase A(2) (PLA(2)), leading to increased inflammatory phospholipid metabolite accumulation, which may propagate the inflammatory process. We stimulated human bladder microvascular endothelial cells with thrombin or tryptase and measured the activation of PLA(2) and the production of multiple membrane phospholipid-derived inflammatory mediators. Thrombin and tryptase stimulation resulted in activation of a Ca(2+)-independent PLA(2), leading to increased release of arachidonic acid and prostacyclin and increased production of platelet-activating factor. These responses were blocked completely by pretreatment of human bladder microvascular endothelial cells with the Ca(2+)-independent PLA(2)-selective inhibitor bromoenol lactone. The combination of increased prostacyclin and platelet-activating factor in the bladder circulation may result in vasodilation and increased polymorphonuclear leukocyte adherence to the endothelium and may facilitate recruitment of polymorphonuclear leukocytes to the bladder wall of patients with interstitial cystitis.
authors.affiliation: Dept. of Pathology, Saint Louis Univ. School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Rickard
authors.forename: Craig
authors.initials: C
authors.lastname: Portell
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Kell
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Vinson
authors.forename: Jane
authors.initials: J
authors.lastname: McHowat
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003556:Cystitis / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011464:Epoprostenol / Q000378:metabolism; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D008833:Microcirculation / Q000166:cytology / Q000201:enzymology; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000032:analysis; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D053802:Tryptases; D001743:Urinary Bladder / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
chemical_list: D006490:Hemostatics; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D016718:Arachidonic Acid; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2; D012697:Serine Endopeptidases; D013917:Thrombin; D053802:Tryptases; D002118:Calcium