期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 47, 期 3, 页码 241-249出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.04.017
关键词
Autoimmune disease; Interstitial pneumonia; Superantigen; Lipid-derived carbon-centered free radical; ESR spin trapping; Free radicals
资金
- Intramural NIH HHS [Z99 ES999999, Z01 ES050117-17] Funding Source: Medline
We studied the free radical generation involved in the development of interstitial pneumonia (IP) in an animal model of autoimmune disease. We observed an electron spin resonance (ESR) spectrum of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract Of lungs in autoimmune-prone mice after intratracheal instillation of staphylococcal enterotoxin B. The POBN adducts detected by ESR were paralleled by infiltration of macrophages and neutrophils into the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride, which significantly Suppressed the radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidise (XO) inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration into the alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived carbon-centered free radical production is important in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP. Published by Elsevier Inc.
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