ACTIVATION OF HUMAN MONOCYTE-MACROPHAGE CYTOTOXICITY BY IL-2 IFN-GAMMA IS LINKED TO INCREASED EXPRESSION OF AN ANTITUMOR RECEPTOR WITH SPECIFICITY FOR ACETYLATED MANNOSE/

Spontaneous cytotoxicity of human monocytes (purity: 92-95%) against K 562 tumor cells was only observed in 31% healthy donors but, in the pr esence of rhamnogalacturonan (500 ng/ml), enhanced cytotoxicity was re corded for 79% (n = 14) of the donors. Monocytes activated by culturin g with interleukin-2 and/or IFN(gamma) showed increased antitumor cyto toxicity against K562 tumor cells in 86% (n = 21) of the donors exhibi ting additional increases in specific cytotoxicity when the cytotoxici ty assays were carried out in the presence of rhamnogalacturonan. Incr eases of monocyte cytotoxicity achieved by activation with cytokines c oincided with increased formation of monocyte/tumor cell conjugates. S imilarly, increased monocyte cytotoxicity mediated by rhamnogalacturon an also correlated with increased monocyte/tumor cell conjugate format ion most likely due to effector cell/target cell bridging as was origi nally described for rhamnogalacturonan interacting with CD56+ natural killer or lymphokine-activated killer cells and tumor cells. The chemo specificity of the monocyte-based receptors responsible for cytotoxici ty and for monocyte/tumor cell conjugate formation, as well as for the ir rhamnogalacturonan-mediated enhancements, appears to be identical s ince all these effects could be inhibited in a dose-dependent manner b y partially deacetylated (60%) mannose pentaacetate.