Summary
Peritoneal macrophages elicited by Lactobacillus casei YIT9018 (LCEPM) were incubated in culture for 18 h with L. casei; the culture supernatant (LCM) was then harvested and tested for its ability to increase the cytostatic activity of resident peritoneal macrophages (RPM) and LCEPM. Treatment of RPM with LCM induced activation of macrophages to a cytostatic state against L929, Colon 26, P815, P388D1 and L1210 cells. A combination of recombinant human tumor necrosis factor (rhTNF), recombinant mouse TNF (rmTNF), recombinant human interleukin-1 (rhIL-1) or bacterial lipopolysaccharide with recombinant mouse interferon γ (rmIFN-γ) resulted in the synergistic induction of cytostatic activity in RPM. Recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) plus rhTNF increased the cytostatic activity of RPM a little but rmGM-CSF or rhTNF combined with rhIL-1 or alone had no effect. The effect of LCM on RPM was not inhibited by polymyxin B, anti-mTNF antiserum or below 20 U/ml monoclonal anti-rmIFN-γ antibody (anti-rmIFN-γ) but was inhibited by more than 40 U/ml anti-rmIFN-γ, and LCM did not have any interferon antiviral activity. These results suggest that the cytostatic activity of RPM was augmented by the LCM, and that the effect of the LCM may be not due to IFN-γ, TNF, GM-CSF, IL-1 or a small amount of contaminating lipopolysaccharide.
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References
Adams DO, Hamilton TA (1984) The cell biology of macrophage activation. Annu Rev Immunol 2:283
Aggarwal BB, Eesaulu TE, Hass PE (1985) Characterization of receptors for human tumor necrosis factor and their regulation by gamma-interferon. Nature 31:665
Beulter BD, Greenwald D, Hulmes JD, Chang M, Pan YCE, Mathison J, Ulevitch R, Cerami A (1985) Identity of tumor necrosis factor and the macrophage-secreted factor cachectin. Nature 316:552
Deker T, Lohmann-Matthes ML, Gifford GE (1987) Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic macrophages. J Immunol 138:957
Epstein LB, McManus NH, Herbert SJ, Woods-Hellman J, Oliver DG (1981) Microtiter assay for antiviral effects of human and murine interferon utilizing a vertical light path photometer for quantitation. In: Adams DO, Edelson P, Koren H. (ed) Methods for studying mononuclear phagocytes. Academic Press, New York, p 619
Feinman R, Henrikson-DeStefance D, Tsujimoto M, Vilcek J (1987) Tumor necrosis factor is an important mediator of tumor cell killing by human monocytes. J Immunol 138:635
Hashimoto S, Nomoto K, Matsuzaki T, Yokokura T, Mutai M (1984) Oxygen radical production by peritoneal macrophages and Kupffer cells elicited with Lactobacillus casei. Infect Immun 44:61–67
Hashimoto S, Nomoto K, Nagaoka M, Yokokura T (1987) In vitro, in vivo release of cytostatic factors from Lactobacillus casei-elicited peritoneal macrophages after stimulation with tumor cells and immunostimulants. Cancer Immunol Immunother 24, 1
Hashimoto S, Nagaoka M, Yokokura T, Mutai M (1988) Correlation of susceptibility and cytostatic factor-inducing activity of tumor cells to peritoneal macrophages: the role of concanavalin A-binding glycopeptide. Scand J Immunol 27:261
Hori K, Ehrke MJ, Mace K, Maccubbin P, Doyle MJ, Otuka Y, Mihich E (1987) Effect of recombinant human tumor necrosis factor on induction of murine macrophage tumoricidal activity. Cancer Res 47:2793
Hori K, Ehrke MJ, Mace K, Mihichi E (1987) Effect of recombinant tumor necrosis factor on tumoricidal activation of murine macrophages: synergism between tumor necrosis factor and γ-interferon. Cancer Res 47:5868
Kato I, Kobayashi S, Yokokura T, Mutai M (1981) Antitumor activity of Lactobacillus casei in mice. Gann 72:517
Kato I, Yokokura T, Mutai M (1983) Macrophage activation by Lactobacillus casei in mice. Microbiol Immunol 27:611
Kato I, Yokokura T, Mutai M (1985) Induction of tumoricidal peritoneal exudated cells by administration of Lactobacillus casei. Int J Immunopharmacol 7:103
Kleinerman ES, Erickson KL, Schroit AJ, Fogler WE, Fidler IJ (1983) Activation of tumoricidal properties in human blood monocytes by liposomes containing lipophilic muramyl tripeptide. Cancer Res 43:2010
Koeffler HP, Gasson J, Ranyard J, Souza L, Shepard M, Munker R (1987) Recombinant human TNF alpha stimulates production of granulocyte colony-stimulating factor. Blood 70:55
Leu RW, Herriott MJ (1987) Triggering of interferon primed macrophages by various known complement activators for nonspecific tumor cytotoxicity. Cell Immunol 106:114
Mannel DN, Moor RN, Mergenhogen SE (1980) Macrophages as a source of tumoricidal activity (tumor necrosis factor). Infect Immun 30:523
Marino PA, Adams DO (1982) The capacity of activated murine macrophages for augmented binding of neoplastic cells: analysis of induction by lymphokine containing MAF and kinetics of the reaction. J Immunol 128:2816
Meltzer MS (1981) Tumor cytotoxicity by lymphokine-activated macrophages: development of macrophage tumoricidal activity requires a sequence of reactions. In: Pick E (ed) Lymphokines 3, Academic Press, New York, p 319
Meltzer MS (1981) Macrophage activation tumor cytotoxicity: characterization of priming and trigger signals during lymphokine activation. J Immunol 127:179
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: Applications to proliferation and cytotoxicity assay. J Immunol Methods 65:55
Nathan CF (1986) Secretory products of macrophages. J Clin Invest 79:319
Nawroth P, Stern DM (1986) Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 163:740
Pace JL, Russell SW, Torres BA, Johnson HM, Gray PW (1983) Recombinant mouse γ-interferon induces the priming step in macrophage activation for tumor cell killing. J Immunol 130:2011
Ralph P, Nakoinz I (1987) Stimulation of macrophage tumoricidal activity by the growth and differentiation factor CSF-1. Cell Immunol 105:270
Robinson BWS, McLemore TL, Crystal RG (1985) Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis. J Clin Invest 75:1488
Semb H, Peterson J, Tavermier J, Oliverona T (1987) Multiple effects of tumor necrosis factor on lipoprotein lipase in vivo. J Biol Chem 262:8390
Shimizu T, Nomoto K, Yokokura T, Mutai M (1987) Role of colony-stimulating activity in antitumor activity of Lactobacillus casei in mice. J Leukocyte Biol 42:204
Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB (1985) Cloning and expression in Escherichia coli of the gene for human tumor necrosis factor. Nature 313:803
Stutman O, Cuttito MJ (1980) Genetic influences affecting natural cytotoxic (NC) cells in mice. In: Herberman RB (ed) Natural cell-mediated immunity against tumors. Academic Press, New York, p 431
Sugarman B, Aggarwal BB, Hass PE, Figari IS, Palladino MA, Jr, Separd HM (1985) Recombinant human tumor necrosis factor: transformed cells in vitro. Science 230:943
Tada H, Shino O, Kuroshima K, Koyama M, Tukamoto K (1986) An improved colorimetric assay for interleukin 2. J Immunol Methods 93:151
Torti FM, Dieckman B, Beutler B, Cerami A, Ringold GM (1985) A macrophage factor inhibits adipocyte gene expression: An in vitro model of cachexia. Science 229:867
Urban JL, Shepard HM, Rothstein JL, Sugarman BJ, Sheriber H (1986) Tumor necrosis factor: potent effector molecule for tumor cell killing by activated macrophages. Proc Natl Acad Sci USA 83:5233
Warren MK, Ralph P (1986) Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumor necrosis factor, and colony stimulating activity. J Immunol 137:2281
Yamazaki S, Onishi E, Enami K, Natori K, Kohaze M, Sakamoto H, Tanouchi M, Hayashi H (1986) Proposal of standardized methods and reference for assaying recombinant human tumor necrosis factor. Jpn J Med Sci Biol 39:105
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Hashimoto, S., Nagaoka, M., Hayashi, K. et al. Role of culture supernatant of cytotoxic/cytostatic macrophages in activation of murine resident peritoneal macrophages. Cancer Immunol Immunother 28, 253–259 (1989). https://doi.org/10.1007/BF00205234
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DOI: https://doi.org/10.1007/BF00205234