Submitted on August 5, 2004
Accepted on November 17, 2004
Protease activated receptor stimulation activates a calcium-independent phospholipase A2 in bladder microvascular endothelial cells
Alice Rickard1, Craig Portell1, Pamela J. Kell1, Suzanne M. Vinson1, and Jane McHowat1*
1 Department of Pathology, Saint Louis University, St. Louis, MO, USA
* To whom correspondence should be addressed. E-mail: jane.mchowat{at}tenethealth.com.
Increased mast cell numbers and mast cell activation is one of the prevalent etiologic theories for interstitial cystitis (IC), 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 that may propagate the inflammatory process. We stimulated human bladder microvascular endothelial cells (HBMEC) with thrombin or tryptase and measured PLA2 activation and the production of multiple membrane phospholipid-derived inflammatory mediators. Both thrombin and tryptase stimulation resulted in activation of a calcium-independent phospholipase A2 (iPLA2), leading to an increase in
arachidonic acid and prostacyclin (PGI2) release and increased production of platelet activating
factor (PAF). These responses were all blocked completely by pretreatment of HBMEC with the iPLA2-selective inhibitor bromoenol lactone (BEL). The combination of increased PGI2 and
PAF in the bladder circulation may result in vasodilation and increased polymorphonuclear leukocytes (PMN) adherence to the endothelium and may facilitate recruitment of PMNs to the bladder wall of IC patients.
