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Mycoplasma capricolum membranes induce tumor necrosis factor α by a mechanism different from that of lipopolysaccharide

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Summary

Heat-inactivated (60°C, 45 min)Mycoplasma capricolum strain JR cells activate murine macrophages to secrete high levels of tumór necrosis factor α (TNFα) and to lyse tumor target cells efficiently. Fractionation of the intactM. capricolum cells, obtained from cells harvested at the exponential phase of growth, shows that their capacity to induce TNFα secretion by macrophage resides exclusively in the membrane fraction. The macrophage-mediated cytolysis following activation byM. capricolum membranes was significantly inhibited by specific anti-recombinant murine TNFα antibodies.M. capricolum membranes are a potent inducer of TNFα as the commonly used bacterial lipopolysaccharide, indicated by their doseresponse curve for macrophage activation. Our study further showed thatM. capricolum membranes and lipopolysaccharide synergize to augment TNFα secretion by C57BL/6-derived macrophages markedly. Moreover, lipopolysaccharide-unresponsive C3H/HeJ-derived macrophages, were pronouncedly activated byM. capricolum membranes, which do not contain lipopolysaccharide. These findings suggest that the mechanism by whichM. capricolum membranes activate macrophages differs from that of lipopolysaccharide. Results of preliminary experiments show that human monocytes as well secrete TNFα following activation byM. 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.

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Authors and Affiliations

  1. The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, P.O. Box 1172, 91010, Jerusalem, Israel

    Talia Sher & Ruth Gallily

  2. The Department of Membrane and Ultrastructure Research, The Hebrew University-Hadassah Medical School, P.O. Box 1172, 91010, Jerusalem, Israel

    Shlomo Rottem

Authors
  1. Talia Sher
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  2. Shlomo Rottem
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  3. Ruth Gallily
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Additional information

This study was supported by the Ernst David Bergmann Fund of the Hebrew University, Jerusalem, the Concern II Foundation for Cancer Research, Los Angeles, and the Society of Research Associates of the Lautenberg Center

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Sher, T., Rottem, S. & Gallily, R. Mycoplasma capricolum membranes induce tumor necrosis factor α by a mechanism different from that of lipopolysaccharide. Cancer Immunol Immunother 31, 86–92 (1990). https://doi.org/10.1007/BF01742371

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  • DOI: https://doi.org/10.1007/BF01742371

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