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Analysis of Nitric Oxide Synthase and Nitrotyrosine Expression in Human Pulmonary Tuberculosis

Department of Medicine, Program in Cell Biology, National Jewish Medical and Research Center, Denver Veterans Administration Medical Center, Division of Pulmonary Sciences and Critical Care Medicine, and Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Edward D. Chan, M.D., K613e, Goodman Building, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: chane{at}njc.org

The role of nitric oxide (NO) in the host-defense against human tuberculosis (TB) is controversial. Although experimental evidence indicates that NO may play an important role in controlling TB, its expression in human tuberculous lungs has not been systematically characterized. We therefore investigated the expression of NO synthases (NOS) and of nitrotyrosine, the latter a marker of NO expression, in surgically resected lungs of eight patients with TB. Immunohistochemical and morphometric analyses revealed that, compared with control subjects, inducible NOS, endothelial NOS, and nitrotyrosine, but not neuronal NOS, were significantly elevated in the inflammatory zone of the tuberculous granulomas, and in the nongranulomatous pneumonitis zone. Tumor necrosis factor- (TNF-) was also significantly increased in tuberculous lungs and was principally localized to the necrotic, and to a lesser extent, the inflammatory and fibrotic areas of the granulomas. The NOS isoforms, nitrotyrosine, and TNF- were expressed by the epithelioid macrophages and giant cells within the granulomas and in alveolar macrophages and epithelial cells in pneumonitis areas. This descriptive study provides evidence that in human TB, NOS isoenzymes and NO are present in specialized areas of the tuberculous granulomas; their precise role in human TB remains to be determined.

Key Words: Mycobacterium tuberculosis • nitric oxide • reactive nitrogen intermediates • immunohistochemistry • morphometry

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