Glucan, a beta 1,3-linked
polyglucose, is an effective macrophage activating and
tumor-inhibitory agent. Previous studies indicate that
glucan enhances macrophage-mediated tumoricidal activity. The present study was designed to examine the ability of
glucan to enhance the production of
tumor cell cytotoxic/
cytostatic factor(s) designated, because of their macrophage origin, as macrophage cytotoxic factor(s) (MCF). Resting splenic macrophages in culture for 20 h secreted detectable levels of MCF. Coincubation of macrophages with bacterial
endotoxin lipopolysaccharide (LPS) resulted in an enhancement of MCF production, compared to resting macrophages.
Glucan-activated macrophages were more effective in producing MCF than both resting and LPS-activated macrophages. The MCF was cytotoxic to certain tumor cell lines at high concentrations and
cytostatic at lower concentrations. The MCF was not significantly cytotoxic to N3T3 or BC/Sk murine fibroblasts, denoting specificity in response. Loss of MCF activity occurred following coincubation of macrophage culture supernatant with
adenocarcinoma cells but not with normal fibroblasts. The MCF activity eluted at 38,000 and 84,000 daltons following column chromatographic analysis, and was heat labile at 100 degrees C but not 56 degrees C. In addition, MCF activity was diminished by
protease inhibitors and
antisera against
tumor necrosis factor. Induction of MCF secretion may be an additional mechanism of
glucan-induced antitumor activity.