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 K562 tumor cells was only observed in 31% healthy donors but, in the presence of rhamnogalacturonan (500 ng/ml), enhanced cytotoxicity was recorded for 79% (n = 14) of the donors. Monocytes activated by culturing with interleukin-2 and/or IFN gamma showed increased antitumor cytotoxicity against K562 tumor cells in 86% (n = 21) of the donors exhibiting additional increases in specific cytotoxicity when the cytotoxicity assays were carried out in the presence of rhamnogalacturonan. Increases of monocyte cytotoxicity achieved by activation with cytokines coincided with increased formation of monocyte/tumor cell conjugates. Similarly, increased monocyte cytotoxicity mediated by rhamnogalacturonan also correlated with increased monocyte/tumor cell conjugate formation most likely due to effector cell/target cell bridging as was originally described for rhamnogalacturonan interacting with CD56+ natural killer or lymphokine-activated killer cells and tumor cells. The chemospecificity of the monocyte-based receptors responsible for cytotoxicity and for monocyte/tumor cell conjugate formation, as well as for their rhamnogalacturonan-mediated enhancements, appears to be identical since all these effects could be inhibited in a dose-dependent manner by partially deacetylated (60%) mannose pentaacetate.
Zhu
H G
HG
Friedrich-Miescher-Laboratorium, Max-Planck-Gesellschaft, Tübingen, Germany.
Zollner
T M
TM
Klein-Franke
A
A
Anderer
F A
FA
D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology; D008358:Mannose / Q000031:analogs & derivatives / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D010368:Pectins / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000276:immunology*
D007155:Immunologic Factors; D007376:Interleukin-2; D011971:Receptors, Immunologic; C082603:acetylmannose receptor; D007371:Interferon-gamma; D010368:Pectins; D008358:Mannose