Induction of nitric oxide synthase is a necessary precondition for expression of tumor necrosis factor-independent tumoricidal activity by activated macrophages.
Various bacteria and bacterial products induce in pure, lymphocyte-free bone marrow-derived mononuclear phagocytes (BMMø) the generation of tumor necrosis factor, nitric oxide (NO) synthase, NO and nitrite (NO2-), the flow of L-arginine to citrulline, and tumoricidal activity. The flow of L-arginine to citrulline and formation of NO/NO2- on the one hand and expression of tumoricidal activity were not always closely related; however, these parameters were suppressed in a dose-dependent manner by the flavoprotein inhibitor, diphenyleneiodonium (DPI) and the L-arginine analogue, NG-monomethyl-L-arginine (NMMA). The findings support the concept of a central role of the NO synthase pathway in the generation of tumor necrosis factor-independent tumoricidal activity by activated macrophages but the exact conditions which enable the transfer of the lytic principle from the effector to the target cell remain to be elucidated.
Keller
R
R
Immunobiology Research Group, Institute for Immunology and Virology, University of Zurich, Switzerland.
Bassetti
S
S
Keist
R
R
Mülsch
A
A
Klauser
S
S
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001853:Bone Marrow / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002956:Citrulline / Q000378:metabolism; D004351:Drug Resistance; D013293:Enterococcus faecalis; D004926:Escherichia coli; D007700:Kinetics; D008070:Lipopolysaccharides; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012515:Mast-Cell Sarcoma; D001936:Moraxella catarrhalis; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010457:Peptidoglycan / Q000302:isolation & purification; D010586:Phagocytes / Q000166:cytology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D019323:omega-N-Methylarginine
D008070:Lipopolysaccharides; D009573:Nitrites; D009861:Onium Compounds; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D002956:Citrulline; C007517:diphenyleneiodonium; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases