1. Neutrophil adherence to bladder microvascular endothelial cells following platelet-activating factor acetylhydrolase inhibition.
- Author
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Vinson SM, Rickard A, Ryerse JS, and McHowat J
- Subjects
- Arachidonic Acids therapeutic use, Cell Adhesion drug effects, Cells, Cultured, Cystitis drug therapy, Cystitis etiology, Endothelial Cells cytology, Humans, Organophosphonates therapeutic use, Phospholipases A antagonists & inhibitors, Phospholipases A physiology, Platelet Activating Factor biosynthesis, 1-Alkyl-2-acetylglycerophosphocholine Esterase antagonists & inhibitors, Arachidonic Acids pharmacology, Endothelial Cells metabolism, Enzyme Inhibitors pharmacology, Neutrophils physiology, Organophosphonates pharmacology, Urinary Bladder blood supply
- Abstract
Interstitial cystitis (IC) is an inflammatory bladder condition of unknown etiology. Tryptase released from elevated numbers of activated mast cells is a proposed mediator of the inflammatory process in IC. We have previously shown that tryptase increases human bladder microvascular endothelial cell (HBMEC) calcium-independent phospholipase A(2) (iPLA(2)) activity, resulting in the production of multiple biologically active phospholipid metabolites, including platelet-activating factor (PAF), that can mediate inflammation. Because the design of selective PLA(2) inhibitors may provide a useful therapeutic strategy to reduce the inflammatory process in IC, we tested several frequently used PLA(2) inhibitors on PAF production in tryptase-stimulated HBMEC. Among the inhibitors tested, methyl arachidonyl fluorophosphonate (MAFP) was found to be a potent inhibitor of PAF-acetylhydrolase activity. Pretreatment of HBMEC with MAFP significantly increased PAF production in both unstimulated and tryptase-stimulated cells. In addition, MAFP pretreatment of tryptase-stimulated HBMEC increased both surface expression of P-selectin and polymorphonuclear leukocyte adherence to the HBMEC monolayer. These effects suggest that MAFP has a proinflammatory effect, irrespective of its ability to inhibit PLA(2).
- Published
- 2005
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