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Treatment of ICR mice i.p., with the antitumor polysaccharide (1 leads to 3)-beta-D-glucan (TAK-N) or its carboxymethyl derivative (CM-glucan) rendered macrophages cytotoxic to L5178Y lymphoma cells in vitro. The ability of macrophages to inhibit tumor cell proliferation appeared on days 4 and 9 after the injections of TAK-N and CM-glucan, respectively. Peritoneal macrophages from normal untreated mice were not cytotoxic. On in vitro incubation with serum from mice treated, with the glucans, peritoneal macrophages from normal untreated mice became cytotoxic to tumor cells. This activating effect appeared transitorily in the serum on days 2-4 and 9-10 after administrations of TAK-N and CM-glucan, respectively, to mice. Neither the glucans alone, nor serum from untreated mice induced cytotoxicity of normal mouse peritoneal macrophages in vitro. On fractionation of mouse serum obtained on day 4 after injection of TAK-N at a dose of 80 mg/kg, two in vitro activators of normal macrophage were obtained: one was a peptide (mol. wt., 4,500 daltons), and the other was probably a peptidoglycan (mol. wt., 9000 daltons).

Effect of serum from mice treated with antitumor polysaccharide on expression of cytotoxicity by mouse peritoneal macrophages.