MACROPHAGE-ACTIVATING FACTOR EXTRACTED FROM MYCOPLASMAS

Mycoplasmas (M. gallisepticum, chicken mycoplasmas), in concert with interferon gamma (IFN-gamma), were effective in activating macrophages (M-theta to be tumoricidal. The M-theta-activating capacity of mycoplasmas was maintained after treatment with heat, 0.1 M NaOH, 1 M HCl, or trypsin. M-theta-activating factor was extracted from mycoplasmas with chloroform/methanol and water (Mf-B). Mf-B was also effective in activating M-theta in the presence of IFN-gamma. The threshold dose of Mf-B for M-theta of ordinary C3H/He mice and that for those of C3H/HeJ mice, the latter being known to be low responders to bacterial lipopolysaccharide, were actually the same. This seems to indicate that the effectiveness of Mf-B was not attributable to possibly contaminating lipopolysaccharides, and that the pathway of activity of Mf-B is different from that of lipopolysaccharides. Since the M-theta-activating principle was only a very small part of Mf-B, we have not yet succeeded in identifying it, but there was no evidence that it was protein, nucleic acid, sugar, or lipid. The cytotoxicity of M-theta activated by Mf-B plus IFN-gamma was dependent on L-arginine in the culture, suggesting that arginine metabolites are involved in M-theta cytotoxicity. Mf-B induced a small amount of tumor necrosis factor in M-theta, and this induction was markedly enhanced by IFN-gamma.