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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/F714    most recent 00288.2004v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Rickard, A. Articles by McHowat, J. Search for Related Content PubMed PubMed Citation Articles by Rickard, A. Articles by McHowat, J.

Protease-activated receptor stimulation activates a Ca²⁺-independent phospholipase A₂ in bladder microvascular endothelial cells

Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri

Submitted 5 August 2004 ; accepted in final form 17 November 2004

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 A₂ (PLA₂), 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 PLA₂ and the production of multiple membrane phospholipid-derived inflammatory mediators. Thrombin and tryptase stimulation resulted in activation of a Ca²⁺-independent PLA₂, 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 Ca²⁺-independent PLA₂-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.

interstitial cystitis; inflammation