Suppression of pulmonary hypersensitivity granulomas in mice by superoxide dismutase.
Pulmonary hypersensitivity granulomas were induced in immunized mice by the intratracheal injection of antigen-coupled agarose beads. Foreign body lung granulomas were induced in mice by the intratracheal injection of dextran beads. Both lesions developed within 1 day, reached peak intensity within 3 days, and gradually declined in size thereafter. Hypersensitivity granulomas were much larger than foreign body lesions. The lung extracts prepared from mice with hypersensitivity lung granulomas, but not foreign body lesions, contained high levels of superoxide dismutase (SOD) and thiobarbiturate-reactive substances including lipid peroxides. SOD activity and levels of thiobarbiturate-reactive substances in the extracts correlated with sizes of hypersensitive lesions. Hypersensitivity granulomas, but not foreign body lesions, were inhibited by the administration of recombinant human SOD (rh-SOD). Thiobarbiturate-reactive substances were decreased in the lung extracts of mice bearing hypersensitivity granulomas injected with rh-SOD. These results suggest that reactive oxygen intermediates such as superoxide anion may play an important role in the development of hypersensitivity granulomas and that rh-SOD is capable of inhibiting the lesions by its antioxidant action.
Kasama
T
T
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Kobayashi
K
K
Yamagata
N
N
Matsuda
T
T
Kasahara
K
K
Takahashi
T
T
D000118:Acetylglucosaminidase / Q000032:analysis; D000818:Animals; D005260:Female; D006099:Granuloma / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D008054:Lipid Peroxides / Q000032:analysis; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000032:analysis / Q000494:pharmacology*
D008054:Lipid Peroxides; D013482:Superoxide Dismutase; D000118:Acetylglucosaminidase; D010100:Oxygen