Correlation between Tumor Cell Cytotoxicity and Serine Protease Activity of Peritoneal Macrophages from Mice Treated with Bakers' Yeast Mannans

Abstract

Peritoneal exudate cells (PEC) from C3H/He mice given bakers' yeast mannans, WNM and WAM025, showed marked cytolytic activity against MM46 tumor cells in vitro. Because the cytotoxicity of the PEC was strongly inhibited by actinomycin D, it was assumed that the cytolytic factor was a proteinous material (s). Of the macrophages and polymorphonuclear leucocytes (PMN) separated from the PEC, only the former cells were found to display cytolytic activity. Quinacrine, a phospholipase A₂, inhibitor, and sodium azide, a myeloperoxidase inhibitor, did not reduce the cytotoxicity of macrophages from mice treated with acidic mannan (WAM025). In contrast, diisopropylfluorophosphate, a serine protease inhibitor, inhibited the cytolysis of the MM46 target cells by WAM025-treated macrophages. Chymostatin, a chymotrypsin inhibitor, and elastatinal, an elastase inhibitor, also inhibited the cytolytic effect. It is therefore concluded that serine proteases secreted into the medium from the macrophages activated by mannans participated in the cytolytic destruction of neoplasmic cells.