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Recruitment of inflammatory cells to the bladder endothelium exposed to cigarette smoke extract (669.1)
Author(s) -
Marentette John,
McHowat Jane
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.669.1
Subject(s) - platelet activating factor , interstitial cystitis , medicine , endothelium , pharmacology , receptor , inflammation , chemistry , immunology , endocrinology , urinary system
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating disease of unknown etiology. Several risk factors are associated with IC/PBS including smoking, weight and diet. Platelet activating factor (PAF) plays a role in inflammatory cell recruitment to the endothelium and we have shown that PAF metabolism by PAF‐acetylhydrolase (PAF‐AH) is inhibited by cigarette smoke. We propose that cigarette smoking inhibits bladder endothelial PAF‐AH activity and contributes directly to inflammatory cell recruitment in the bladder wall. Incubation of human bladder microvascular endothelial cells (HBMEC) with cigarette smoke extract (CSE, 20 µg/mL) resulted in a significant inhibition of PAF‐AH activity with increased PAF accumulation and polymorphonuclear leukocyte (PMN) adherence. Pretreatment of HBMEC with (S)‐bromoenol lactone to inhibit calcium‐independent phospholipase A 2 β and PAF production prior to CSE incubation lead to a significant reduction in PMN adherence to the bladder endothelium. Similarly, pretreatment of PMN with PAF receptor antagonists (WEB 4086 or Ginkgo biloba ) prior to CSE caused a significant reduction in PMN adherence. We propose that targeting endothelial cell PAF production or blocking the PAF receptor may represent novel therapies for management of IC/PBS patients, particularly smokers. Grant Funding Source : Supported by a President's Research Fund, Saint Louis University grant