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Independence of the Pattern of Early Cytokine Release From Autoregulation by Nitric Oxide
Author(s) -
Tucker Stanley D.,
Sivaramakrishnan Mathoor R.,
Klostergaard Jim,
LopezBerestein Gabriel
Publication year - 1991
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.50.5.509
Subject(s) - nitric oxide , lipopolysaccharide , biology , nitrite , cytotoxic t cell , tumor necrosis factor alpha , cytokine , incubation , cytotoxicity , arginine , effector , biochemistry , microbiology and biotechnology , immunology , endocrinology , in vitro , amino acid , nitrate , ecology
Abstract The L‐arginine‐dependent tumor cell cytotoxicity produced by activated macrophages (Mφ) may be mediated either directly by production of nitric oxide (NO), or by induction of NO synthesis in the tumor cell. The influence of Mφ NO synthesis on the release of soluble cytotoxic mediators was investigated in this study. The synthesis of Mφ NO, measured as nitrite, was detected 6 h after lipopolysaccharide (LPS)‐triggering and reached a peak level by 44 h. A concurrent decrease in Mφ viability beginning at 18 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 N G ‐monomethyl‐L‐arginine (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‐γ), 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‐triggering. The peak level obtained for each effector molecule was influenced by the media in which the Mφ was incubated; however, no correlation was detected between the level of cytokines produced and the synthesis of nitrite by the Mφ indicating that NO synthesis has no inhibiting effect on the initial burst of cytotoxic factors released.