HUMAN MONOCYTES ARE STIMULATED FOR NITRIC-OXIDE RELEASE IN-VITRO BY SOME TUMOR-CELLS BUT NOT BY CYTOKINES AND LIPOPOLYSACCHARIDE

Nitric oxide (NO) has been recently identified as a potent mediator of tumoricidal activity of activated macrophages. Macrophages can be act ivated for tumor cell killing by microbial products, including lipopol ysaccharide (LPS) and various cytokines. Here we report that in contra st to mouse macrophages, human peripheral blood monocytes stimulated w ith cytokines or LPS failed to release NO. Also priming of monocytes w ith interferon-gamma followed by activation with cytokines or LPS did not cause NO secretion. However, monocytes responded with NO productio n to stimulation with some human cancer cells but not with untransform ed cells. NO production by monocytes was inhibited by NG monomethyl-L- arginine, specific inhibitor of NO synthase and emetine, an irreversib le blocker of protein synthesis. This may imply that human monocytes a re unique in their restricted capacity to produce NO following interac tion with some tumor cells, but not with other stimulators, and in thi s respect they may be able to distinguish between malignant and normal cells.