Lysozyme enhances monocyte-mediated tumoricidal activity: a potential amplifying mechanism of tumor killing.
The mononuclear phagocyte is well established as an in vitro cytotoxic effector cell for certain human tumors. The mechanism(s) for this action remains unclear. Increased levels of lysozyme, a cationic enzyme synthesized in large amounts by mononuclear phagocytes, are associated with increased resistance to transplantable animal tumors. In this study, we provide evidence that human lysozyme, isolated from the urine of leukemic patients, has marked potentiating effects on human monocyte-tumor-cell cytocidal activity. In addition, lysozyme-exposed monocytes incorporate increased quantities of leucine, suggesting that monocytes are capable of amplifying their own metabolic activation by secreting an endogenous constituent. Tri-N-acetyl-glucosamine, a competitive inhibitor for the active site of lysozyme, inhibits cytocidal activity. Conversely, protamine, an extraneous albeit similarly positively charged molecule, increases monocyte-mediated tumor cytotoxicity; this protamine effect is negated by heparin. We conclude that lysozyme, at least partially by its positive charge, is capable of enhancing in vitro monocyte tumor cell cytotoxicity; its in vivo secretion may potentiate monocyte-tumor-cell interaction.
D000117:Acetylglucosamine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006600:Hexosephosphates / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008545:Melanoma / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D009113:Muramidase / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology
D000970:Antineoplastic Agents; D006600:Hexosephosphates; D009113:Muramidase; D007930:Leucine; D000117:Acetylglucosamine