Activated macrophages kill tumour cells by releasing arginase

Abstract

WHEN rodent peritoneal exudate macrophages are exposed to stimuli such as zymosan, bacterial lipopolysaccharide (LPS) or lymphokines they become cytotoxic to a variety of cultured target cells^1,2. The toxic effects of such ‘activated’ macrophages show no immunological specificity but may show a broad selectivity for transformed³ or malignant cells⁴. Furthermore, this cytotoxic activity has been attributed⁴ to a soluble macro-phage product. Kung et al. have shown⁵ that the addition of excess macrophages to mouse mixed leukocyte cultures depletes the culture medium of arginine and thereby suppresses lymphocyte reactivity. This is associated with the appearance of arginase within cultured macrophages. The experiments reported here show that activation of macrophages by zymosan or LPS induces the production and release of arginase and that the cytotoxic activity of the macrophages and of their supernatant media on the target cells is a consequence of arginine deprivation.