Mycoplasma capricolum membranes induce tumor necrosis factor alpha by a mechanism different from that of lipopolysaccharide.
Heat-inactivated (60 degrees C, 45 min) Mycoplasma capricolum strain JR cells activate murine macrophages to secrete high levels of tumor necrosis factor alpha (TNF alpha) and to lyse tumor target cells efficiently. Fractionation of the intact M. capricolum cells, obtained from cells harvested at the exponential phase of growth, shows that their capacity to induce TNF alpha secretion by macrophage resides exclusively in the membrane fraction. The macrophage-mediated cytolysis following activation by M. capricolum membranes was significantly inhibited by specific anti-recombinant murine TNF alpha antibodies. M. capricolum membranes are a potent inducer of TNF alpha as the commonly used bacterial lipopolysaccharide, indicated by their dose-response curve for macrophage activation. Our study further showed that M. capricolum membranes and lipopolysaccharide synergize to augment TNF alpha secretion by C57BL/6-derived macrophages markedly. Moreover, lipopolysaccharide-unresponsive C3H/HeJ-derived macrophages, were pronouncedly activated by M. capricolum membranes, which do not contain lipopolysaccharide. These findings suggest that the mechanism by which M. capricolum membranes activate macrophages differs from that of lipopolysaccharide. Results of preliminary experiments show that human monocytes as well secrete TNF alpha following activation by M. capricolum membranes. Thus, in contrast with the prohibitive toxicity of lipopolysaccharide to animals and humans, M. capricolum membranes, which contain no lipopolysaccharide and are nontoxic in nature, may be of therapeutic value in the treatment of cancer.
Sher
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Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Rottem
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Gallily
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D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009174:Mycoplasma / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha