TY - JOUR
T1 - Independence of the pattern of early cytokine release from autoregulation by nitric oxide
AU - Tucker, S. D.
AU - Sivaramakrishnan, M. R.
AU - Klostergaard, J.
AU - Lopez-Berestein, G.
PY - 1991
Y1 - 1991
N2 - 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 rfactor (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 correlatiion 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.
AB - 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 rfactor (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 correlatiion 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.
KW - IFN-γ
KW - Macrophages
KW - Respiratory inhibition
KW - TNF
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U2 - 10.1002/jlb.50.5.509
DO - 10.1002/jlb.50.5.509
M3 - Article
C2 - 1748844
AN - SCOPUS:0025946108
SN - 0741-5400
VL - 50
SP - 509
EP - 516
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -