title: Bradykinin receptor 2 extends inflammatory cell recruitment in a model of acute gouty arthritis.
abstract: The aim of this study was determine the effect of bradykinin receptor antagonism on MSU crystal-induced chemokine production and leukocyte recruitment. Mice were injected intraperitoneally with monosodium urate (MSU) crystals ± bradykinin B1- or B2 receptor antagonists, Des-Arg-HOE-140 and HOE-140, respectively. MSU crystal-induced chemokine production and leukocyte recruitment in the peritoneum were measured over 24h and B1 and B2 receptor expression on leukocytes and peritoneal membrane was determined by flow cytometry and fluorescence microscopy. Data analysis showed that only B2 receptor antagonism decreased monocyte and neutrophil infiltration 24 h post MSU crystal administration. Decreased leukocyte infiltration was associated with reduced monocyte (CCL2) chemokine levels. MSU crystal-induced damage to the surrounding visceral membrane was also attenuated in the presence of B2 receptor antagonism. Together, these data show that bradykinin receptor 2 plays a role in maintaining MSU crystal-induced leukocyte infiltration and membrane permeability and identify the B2 receptor as a potential therapeutic target for managing inflammation in gout.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Odette M
authors.initials: OM
authors.lastname: Shaw
authors.forename: Jacquie L
authors.initials: JL
authors.lastname: Harper
mesh_terms: D000208:Acute Disease; D000818:Animals; D015210:Arthritis, Gouty / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D014527:Uric Acid / Q000494:pharmacology
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D018932:Chemokine CCL2; D043782:Receptor, Bradykinin B2; D014527:Uric Acid; C065679:icatibant; D001920:Bradykinin