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Journal of Leukocyte Biology 50:509-516 (1991) Independence of the Pattern of Early Cytokine Release From Autoregulation by Nitric Oxide

By Stanley D. Tucker, Mathoor R. Sivaramakrishnan, Jim Klostergaard and Gabriel Lopez-berestein


The L-argmnine-dependent tumor cell cytotoxicity produced by activated macrophages (M4) may be mediated either directly by production of nitric oxide (NO), or by induction of NO synthesis in the tumor cell. The influence of M4 NO synthesis on the release of soluble cytotoxic mediators was investigated in this study. The synthesis of Md NO, measured as nitrite, was detected 6 h after Iipopolysaccharide (LPS)-triggering and reached a peak level by 44 h. A concurrent decrease in M4 viability beginning at 1 8 h after triggering was detected during a period of 72 h in culture. Both the production of NO and loss of viability correlated with the presence of L-arginine in the incubation media and was inhibited by NG monomethyI.L argmnmne (NMA). The medium in which LPS-triggered adherent peritoneal exudate cells were incubated was examined for the presence of tumor necrosis factor (TNF), gamma interferon (IFN--y), and the soluble mediators that induce mitochondrial respiratory inhibition in tumor cells. All of these effector molecules were released at peak levels into the conditioned supernatants within 12 h after LPS-triggerlng. The peak level obtained for each effector molecule was influenced by the media in which the M4 was incubated; however, no correlation was detected between the level of cytokines produced and the synthesis of nitrite by the M4 indicating that NO synthesis has no inhibiting effect on the initial burst of cytotoxic factors released

Topics: Key words, macrophages, respiratory inhibition, TNF, IFN--y
Year: 2013
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