Interferon-gamma/tumour necrosis factor-alpha synergism as a mechanism for enhanced nitric oxide production following in vivo administration of muramyl dipeptide (MDP) to mice.
The aim of the present study was to investigate the role of muramyl dipeptide (MDP) in triggering host non-specific defence mechanisms, namely its influence upon the L-arginine-dependent biotransformation pathways leading to formation of nitric oxide (NO). MDP was applied subcutaneously to mice as one or three daily injections, 300 micrograms MDP each. Production of NO by peritoneal macrophages from these animals or the capability of their splenocytes to render virgin macrophages for enhanced NO production was assayed. It has been found that macrophages from MDP-treated animals produce considerably enhanced amounts of NO and that the splenocytes secrete soluble factors providing all the signals required for induction of NO biosynthesis. Introduction of anti-IFN-gamma or anti-TNF-alpha antibodies into these splenocyte supernatants resulted in complete suppression of inducible NO production by macrophages.
Zídek
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Institute of Pharmacology, Academy of Sciences of the Czech Republic, Prague.
Franková
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D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000494:pharmacology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D007279:Injections, Subcutaneous; D007369:Interferon Inducers / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology* / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D019323:omega-N-Methylarginine
D007369:Interferon Inducers; D008222:Lymphokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases