Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.

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Abstract
Activation of mouse peritoneal exudate macrophages, as evidenced by destruction of the intracellular protozoan parasite Leishmania enriettii, was obtained by incubation with supernates from concanavalin (Con) A-stimulated syngeneic spleen cells. Parasites were not destroyed in macrophages exposed to control media. Supernate-induced activation was independent of the presence of Con A. The activating principle (macrophage activating factor [MAF]) was produced by Con A-stimulated lymphocytes in the presence or absence of serum. In the absence of serum, MAF synthesis was highest at Con A concentrations far below those required in serum-containing media. MAF production was reduced at Con A concentrations of 10 .mu.g/ml or above, probably a result of toxicity of the lectin for lymphocytes. MAF was detectable after 24 h of lymphocyte stimulation and increased up to 72 h; production appeared independent of DNA synthesis. Serum-free MAF was inactive when tested as such on macrophages. Full activity could be restored by addition of ng amounts of [Escherichia coli] endotoxin [etox] or of FCS [fetal calf serum] before assay. Etox potentiated MAF activity in serum-containing supernates. Full intracellular parasite destruction was observed after contact of macrophages with MAF for 20 h. The continuous presence of MAF was not necessary for activation: a 10 h pulse was sufficient to induce macrophages to destroy all intracellular microorganisms within the next 38 h.