Prostaglandins, leukotrienes and PAF selectively modulate lymphocyte subset and eosinophil infiltration into the airways in a murine model of asthma.
The effects of inhibitors of prostaglandins synthesis, indomethacin and nimesulide, or of receptor antagonists of cysteinyl-leukotrienes, MK571 or of platelet activating factor (PAF), WEB2170, were studied on the infiltration of lymphocytes (Tgammadelta, NKT, CD4, CD8 and B cells) and eosinophils into the bronchoalveolar lavage fluid (BALF) in two mouse strains (C57Bl/6 and BALB/c) as well as on bronchial hyperreactivity and mucus production. It was found that indomethacin and nimesulide strongly reduced the number of all cell types analyzed in both mouse strains. MK571 did not affect Tgammadelta or CD4 lymphocytes but reduced the other populations. WEB2170 reduced all lymphocyte subpopulations in both mouse strains. Moreover, the relative numbers of the lymphocyte subsets in the airways and their response to PAF antagonist were strain-dependent. The intensity of bronchoconstriction and mucus production did not correlate with BALF cell types or numbers. The cysteinyl-leukotriene receptor antagonist inhibited eosinophil infiltration and bronchial hyperreactivity, without affecting the Tgammadelta cell subset. Since Tgammadelta cells play a major role in mucosa protection and resolution of lung inflammation, this would represent an additional benefit of cysteinyl-leukotrienes antagonism in asthma.
Landgraf
Richardt G
RG
Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Imunologia, Av. Prof. Lineu Prestes, 1730, CEP 05508-000, São Paulo-SP, Brazil.
Nossi
Daniela F
DF
Sirois
Pierre
P
Jancar
Sonia
S
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D001381:Azepines / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D010972:Platelet Activating Factor / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D015289:Leukotrienes; D010972:Platelet Activating Factor; D011422:Propionates; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011804:Quinolines; D013449:Sulfonamides; D014230:Triazoles; C059141:verlukast; D010047:Ovalbumin; C063964:bepafant; C012655:nimesulide; D007213:Indomethacin