IONIZING-RADIATION POTENTIATES THE INDUCTION OF NITRIC-OXIDE SYNTHASEBY IFN-GAMMA AND OR LPS IN MURINE MACROPHAGE CELL-LINES - ROLE OF TNF-ALPHA/

Macrophages are activated to become cytotoxic by a highly coordinated set of cytokine signals. Ionizing radiation can mimic cytokine signals and lead to enhanced states of activation. We tested the ability of g amma-radiation, alone and,crith interferon-gamma (IFN-gamma) and/or li popolysaccharide (LPS), to induce nitric oxide (NO) production in J774 .1 and RAW264.7 murine macrophages, NO Tvas induced weakly, moderately , or strongly by IFN-gamma alone, LPS alone, or IFN-gamma + LPS, respe ctively. Radiation alone (0.5-50 Gy) did not induce NO, but enhanced N O production in a dose-dependent manner (0.5-5 Gy) when cells were exp osed to IFN-gamma or LPS 24 h post-irradiation, Immunoblots showed par allel induction of nitric oxide synthase (NOS2), Application of anti-t urner necrosis factor alpha (TNF-alpha) antibody before irradiation bl ocked induction of NO by IFN-gamma. We conclude (1) that irradiated ce lls produce more NO in response to either IFN-gamma or LPS and (2) tha t the increase is mediated by induction of TNF-alpha.