In vivo modulation of macrophage tumoricidal activity: enhanced tumor cell killing by peritoneal macrophages from mice given injections of sodium periodate.
Sodium periodate (NaIO4) administered ip to mice was nontoxic and enhanced the in vitro tumoricidal activity of their peritoneal macrophages. The injection ip of 1 ml of 5 mM NaIO4 caused an influx of polymorphonuclear leukocytes (PMN) at 5-24 hours followed by an accumulation of macrophages and disappearance of the PMN at 48-72 hours. These peritoneal macrophages from mice given injections of NaIO4 were noncytotoxic and nontumoricidal in the absence of lipopolysaccharide (LPS), but in the presence of 5-25 ng/ml or more LPS in vitro, they became markedly cytotoxic and cytocidal for tumor cells. Peritoneal macrophages from mice given injections of phosphate-buffered saline became cytotoxic or cytocidal only with amounts of LPS exceeding 100-500 ng/ml in vitro. Like the peritoneal macrophages from BCG-infected mice that demonstrated selective tumor cytotoxicity, macrophages from mice given injections of NaIO4 had minimal lytic activity for nontransformed normal embryo fibroblasts. Thus when given ip to mice, the simple chemical NaIO4, much like complex and heterogeneous biologic preparations such as BCG, caused differentiation of peritoneal macrophages toward the tumoricidal state.
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