Involvement of superoxide and nitric oxide on airway inflammation and hyperresponsiveness induced by diesel exhaust particles in mice.
We previously demonstrated that chronic intratracheal instillation of diesel exhaust particles (DEP) induces airway inflammation and hyperresponsiveness in the mouse, and that these effects were partially reversed by the administration of superoxide dismutase (SOD). In the present study, we have investigated the involvement of superoxide in DEP-induced airway response by analyzing the localization and activity of two enzymes: (1) a superoxide producer, NADPH cytochrome P-450 reductase (P-450 reductase), and (2) a superoxide scavenger, SOD, in the lungs of the exposed mice and controls. P-450 reductase was detected mainly in ciliated cells and clara cells: its activity was increased by the repeated intratracheal instillation of DEP. While CuZn-SOD and Mn-SOD were also present in the airway epithelium, their activity was significantly decreased following DEP instillation. Exposure to DEP doubled the level of nitric oxide (NO) in the exhaled air. DEP exposure also increased the level of constitutive NO synthase (cNOS) in the airway epithelium and inducible NO synthase (iNOS) in the macrophages. Pretreatment with N-G-monomethyl L-arginine, a nonspecific inhibitor of NO synthase, significantly reduced the airway hyperresponsiveness induced by DEP. These results indicate that superoxide and NO may each contribute to the airway inflammation and hyperresponsiveness induced by the repeated intratracheal instillation of DEP in mice.
Lim
H B
HB
Research Team for Health Effects of Air Pollutants, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Ichinose
T
T
Miyabara
Y
Y
Takano
H
H
Kumagai
Y
Y
Shimojyo
N
N
Devalia
J L
JL
Sagai
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000393:Air Pollutants / Q000633:toxicity*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000139:chemically induced; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005648:Fuel Oils / Q000633:toxicity; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced*; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000393:Air Pollutants; D005648:Fuel Oils; D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase; D000109:Acetylcholine