Suppression of mitochondrial respiration and increased glycolysis are charaeteristic features of activated macrophages. We show here that antimycin A, a respiratory inhibiter,inducedinterleukin-1syRthesisandtumericidalactivity without inducing tumer necresis factor er nitric oxide. The induction of tumoricidal actiyity was resista!it te inhibitors of tyrosine-specific protein kinases and intracellular glycoprotein transport. The cognate interaction between macrophages and target cells was not a prerequisite fer the tumericidal activity. In contrast, lipopolysaccharide induced the production of interleukin-1, tumor ilecrosis factor and nitric oxide, the induction of tumoricida} actiyity being sensitive to genistein and brefeldin A. Antimycin A, like lipopolysaccharide, induced the Telease of a cytoplasmic enzyme and apoptosis ef macrophages. Antimycin A showed anti-metastatic activity in vivo. These results suggest that the inhibition of oxidative respiration would induce apoptosis and the resultant release ef soluble effector molecules of macrophages whieh inhibit tumor metastasis in vivo,
A novel mitogen, E-15, which induced blastogenesis of mouse splenocytes, was purified from the culture filtrate of an actinomycete through ethanol precipitation, anion and cation exchange column chromatography, and gel filtration.The producing organism was identified as Nocardia asteroides. Spectronic study demonstrated that it was a polysaccharide. Acid hydrolysis of E-15 yielded glucose and glucosamine. The active substance was eluted at the molecular mass between 90 kDa and 750 kDa on gel filtration. E-15 induced a mitogenic response of mouse splenocytes above 1 /ig/ml and its potency of induction was superior to a lipopolysaccharide that is knownto be a polyclonal B cell-specific mitogen. It showed no toxicity up to lOOjig/ml. The cell surface phenotypes of the blast cells induced by E-15 were analyzed by flow cytometry; they had surface immunoglobulins but no Lyt-2 antigen. Thus it was suggested that E-15 was a B-cell-specific mitogen.
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