[Role of nitric oxide in asthma-like symptoms induced by diesel exhaust particles in mice].
Asthma-like symptoms were induced in mice by repeated intratracheal instillation of diesel exhaust particles. Nitric oxide synthase (NOS) and superoxide dismutase (SOD) in airways were studied with immunocytochemical methods, and the role of nitric oxide was examined with the NOS inhibitor L-NMMA. Diesel exhaust particles increased the staining of cNOS in airway epithelial cells by an anti-cNOS antibody. Macrophages in the mucous membrane were stained clearly, but an anti-iNOS antibody did not stain airway epithelial cells. Diesel exhaust particles caused a 4-fold increase in the total number of macrophages, neutrophils, eosinophils, and lymphocytes in bronchoalveolar lavage fluid. Diesel exhaust particles decreased the staining of Cu, Zn-SOD, and Mn-SOD in epithelial cells by their respective anti-SOD antibodies. Diesel exhaust particles doubled the concentration of nitric oxide in exhaled air. These particles increased respiratory resistance, and this increase was suppressed by pretreatment with the NOS inhibitor L-NMMA. These results suggest that diesel exhaust particles can decrease the scavenging of O2- in airways, which may increase hyperresponsiveness. In mice exposed to diesel exhaust particles, the increase in NOS staining in airway epithelium, the increase in the nitric oxide concentration in exhaled air, and the decrease in respiratory resistance caused by L-NMMA indicate that nitric oxide may increase airway hyperresponsiveness.
Sagai
M
M
National Institute for Environmental Studies, Ibaraki, Japan.
Ichinose
T
T
D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000378:metabolism; D016535:Bronchial Hyperreactivity; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D001335:Vehicle Emissions
D001335:Vehicle Emissions; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase