Tumor necrosis factor as a mediator of Mycoplasma orale-induced tumor cell lysis by macrophages.
We and other investigators have previously demonstrated that mycoplasmas induce macrophage-mediated lysis of tumor cells, but the mechanism responsible for this process had, thus far, not been clarified. We now report that addition of either viable or heat-killed Mycoplasma orale to murine macrophages induces a cytolytic activity which, due to its neutralization by a specific antiserum against murine cloned recombinant tumor necrosis factor (rTNF), was identified as TNF-mediated. Both thioglycollate-elicited peritoneal macrophages and the normal macrophages cloned from our JBM phi 1.1 bone-marrow-derived cell line effectively produced TNF at levels similar to, or higher than, those obtained in the presence of high concentrations of lipopolysaccharide (LPS). Four other mycoplasma species demonstrated a varied capacity to induce TNF production by macrophages. Elevated TNF levels were also observed during macrophage-mediated cytolysis of murine A9 fibrosarcoma cells in the presence of either M. orale or LPS. Addition of the specific antiserum against rTNF at a concentration which neutralized all TNF activity in the co-cultures partially inhibited concomitant A9 cell killing. We can, therefore, conclude that M. orale induces TNF production which is, at least partially, responsible for subsequent tumor cell killing.
Gallily
R
R
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Sher
T
T
Ben-Av
P
P
Loewenstein
J
J
D000818:Animals; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D009174:Mycoplasma / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha