Differential modulation of murine lung inflammation by bradykinin B1 and B2 selective receptor antagonists.
The effect of bradykinin receptor antagonists was studied in a mouse (C57Bl/6) model of allergic lung inflammation. Bradykinin B(2) receptor antagonist HOE-140 (D-Arg-[Hyp(3),Thi(5),Dtic(7)-Oic(8)]bradykinin) or bradykinin B(1) receptor antagonist R-954 (Ac-Orn[Oic(2),alphaMePhe(5),betaD-Nal(7)Ile(8)]des-Arg(9)-bradykinin) were given i.p. to ovalbumin sensitized mice 30 min before antigen challenge. After 24 h, bronchoalveolar lavage was performed for cell analysis and the lungs were removed for evaluation of airway hyperreactivity and histopathology. Treatment with HOE-140 caused a significant increase in bronchoalveolar lavage cell number: eosinophils (182%), neutrophils (98%), lymphocytes CD(4)(+) (192%), CD(8)(+) (236%), B220 (840%), Tgammadelta(+) (194%) and NK1.1(+) (246%). Hyperreactivity and mucus secretion were not significantly affected in this group. Treatment with R-954 significantly reduced eosinophil (79%) and neutrophil (83%) but has no effect on lymphocytes number in bronchoalveolar lavage fluid. Airway hyperreactivity and mucus secretion were reduced by this treatment (84% and 35%, respectively). These results show important modulatory effect of bradykinin B(1) and B(2) receptors on allergic lung inflammation.
Gama Landgraf
Richardt
R
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1730 São Paulo, SP 05508-900, Brazil.
Sirois
Pierre
P
Jancar
Sonia
S
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology
D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C065679:icatibant; D001920:Bradykinin