Glucan stimulates production of antitumor cytolytic/cytostatic factor(s) by macrophages.
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.
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D003603:Cytotoxins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005936:Glucans / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism; D006358:Hot Temperature; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D015846:Monokines; D009374:Neoplasms, Experimental / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha
D003603:Cytotoxins; D005936:Glucans; D006023:Glycoproteins; D015846:Monokines; D011480:Protease Inhibitors; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide