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Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1986 Sep;23(1):41–45. doi: 10.1007/BF00205553

Synergistic induction of cytotoxicity in macrophages by murine interferon-γ and biological response modifiers derived from microorganisms

Shin-ichi Nagao 1,, Keiki Sato 1, Yasuaki Osada 1
PMCID: PMC11038585  PMID: 3094943

Abstract

The ability of recombinant murine interferon-gamma (rMuIFN-γ) to activate murine macrophages with or without several biological response modifiers (BRM), including synthetic muramyl dipeptide derivatives (MDPs), was investigated. Mouse peritoneal macrophages were activated by rMuIFN-γ alone to the cytostatic state, but not the cytolytic state. Other BRM as well as bacterial lipopolysaccharide (LPS), including a lyophilized preparation of an attenuated strain of Streptococcus hemolyticus, a cell wall skeleton of bacillus Calmette-Guerin and synthetic MDPs, were highly active in generating the synergism with rMuIFN-γ. Macrophages were endowed with the cytolytic activities by combinations of rMuIFN-γ and MDP-Lys(L18); the combination of 100U/ml of rMuIFN-γ with 10 ng/ml of MDP-Lys(L18) was sufficient to induce cytolytic activities in macrophages. The synergism was observed when the macrophages primed with rMuIFN-γ were treated with LPS or MDP-Lys(L18), but not when the sequence of treatment was reversed. The cytotoxicity of macrophages induced by rMuIFN-γ with MDP-Lys(L18) was suppressed by priming with MDP-Lys(L18). The suppressive effect was also observed by priming with LPS in combinations of rMUIFN-γ and LPS. The reason for the suppression of macrophage activation by priming with LPS and MDP-Lys(L18) is at present unknown.

Keywords: Cell Wall, Cancer Research, Dipeptide, Suppressive Effect, Peritoneal Macrophage

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