Biological effects of diesel exhaust particles (DEP). III. Pathogenesis of asthma like symptoms in mice.
Chronic airway inflammation, mucus hypersecretion, reversible airway constriction, and bronchial hyperresponsiveness are important pathogenic features of asthma. We found that diesel exhaust particles (DEP) instilled intratracheally and repeatedly to mice (once/week for 16 weeks) caused marked infiltration of inflammatory cells, proliferation of goblet cells, increased mucus secretion, respiratory resistance, and airway constriction. Eosinophils in the submucosa of the proximal bronchi and medium bronchioles increased eightfold following instillation. Eosinophil infiltration was significantly suppressed by pretreatment with polyethyleneglycol-conjugated superoxide dismutase (PEG-SOD). Bound sialic acid concentrations in bronchial alveolar lavage fluids, an index of mucus secretion, increased with DEP, but were suppressed by pretreatment with PEG-SOD. Goblet cell hyperplasia, airway narrowing, and airway constriction also were observed with DEP. Respiratory resistance in the DEP-group to acetylcholine was 11 times higher than in controls, and the increased resistance was significantly suppressed by PEG-SOD pretreatment. These findings suggest that DEP and/or oxygen radicals derived from DEP cause bronchial asthma in mice.
Sagai
M
M
National Institute for Environmental Studies, Research Team for Health Effects of Air Pollutants, Ibaraki, Japan.
Furuyama
A
A
Ichinose
T
T
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001980:Bronchi / Q000473:pathology; D016084:Bronchoconstriction; D004804:Eosinophils / Q000473:pathology; D016166:Free Radical Scavengers; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009093:Mucus / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014132:Trachea / Q000473:pathology / Q000503:physiopathology; D001335:Vehicle Emissions
D016166:Free Radical Scavengers; D001335:Vehicle Emissions; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase