Acute inhibition of inducible nitric oxide synthase but not its absence suppresses asthma-like responses.
In the present study we investigated the lymphocytes infiltration and other parameters of allergic lung inflammation comparing mice submitted to acute suppression of nitric oxide synthesis with mice deficient in inducible nitric oxide synthase (NOS2-/-) gene. At weekly intervals C57Bl/6 mice, wild type and NOS2-/- were sensitized twice with ovalbumin-alumen and challenged twice with ovalbumin aerosol and lungs examined 24 h later. In wild type mice, treatment with nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine-methyl-ester (L-NAME) or aminoguanidine (i.p., 30 min before each ovalbumin challenge) caused a significant decrease in bronchoalveolar lavage cell number: eosinophils (90%), lymphocytes NK1.1+ (70%), Tgammadelta+ (50%), CD4+ (55%), CD8+ (60%) and B220+ (65%). Both inhibitors abolished airway hyperreactivity and significantly reduced mucus secretion (L-NAME 64%; aminoguanidine 58%). Surprisingly, in NOS2-/- mice these parameters of allergic lung inflammation were not significantly different when compared with wild type mice. In addition, treatment of NOS2-/- mice with L-NAME or aminoguanidine did not affect these parameters. Thus, acute inhibition of NOS2 activity inhibits asthma-like responses but absence of NOS2 has no affect.
Landgraf
Richardt G
RG
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Russo
Momtchilo
M
Jancar
Sonia
S
D000818:Animals; D000941:Antigens / Q000032:analysis; D000950:Antigens, Ly; D000954:Antigens, Surface; D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006146:Guanidines / Q000494:pharmacology; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D055651:NK Cell Lectin-Like Receptor Subfamily B; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000276:immunology; D011506:Proteins / Q000032:analysis
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D016085:Bronchoconstrictor Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D004791:Enzyme Inhibitors; D006146:Guanidines; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016210:Methacholine Chloride; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017493:Leukocyte Common Antigens; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester