ABSTRACT
Background: Nitric oxide(NO) has been reproted to play an important role in macrophage-mediated microbicidal capacity for a variety of intracellular pathogens. NO generation is used as an indicator of microbicidal function of macrophages. OBJECTIVE: Our purpose is to investigate the production of NO rom macrophages phagocytized with Mycobacterium leprae or M. leprae phenolic glycolipid-1(PGL-1) for the purpose of elucidating the pathogenesis of leprosy. METHODS: We used a murine macrophage cell line, RAW 264.7. Macrophages were incubated with dead M. leprae or PGL-1, respectively and then treated with interfer n-gamma(IFN-r) and/or tumor necrosis factor-alpha(TNF-a). The release of NO was determined spectrophotometrically by measuring nitrite. RESULTS: M. Leprae and PGL-1 failed to stimulnte NO secretion execept at high bacteria-to-cell rations(50:1)and at the higheat concentrat,ion(100pg/ml) of PGL-1. IFN-r or IFN-r plus TNF-a markedly stimulated macrophages phagocyt,ized with M. leprae or PGL-1 to release NO . CONCLUSION: Defective IFN-r-dependent NO production of macrophages may be an important factor in the pathogenesis of leprosy.