Synergistic action of a plant rhamnogalacturonan enhancing antitumor cytotoxicity of human natural killer and lymphokine-activated killer cells: Chemical specificity of target cell recognition

Journal/Book: Cancer Research 50, 3646-3651. 1990;

Abstract: The spontaneous natural killer (NK) and lymphokine-activated killer(LAK) cytotoxicity of highly purified CD56+CD3- NK cells (90 to 95%)against NK-sensitive and NK-insensitive target cells was drasticallyenhanced when a rhamnogalacturonan contained in a commercially availableViscum album extract was present during 4-h cytotoxicity assays. Thisenhancement correlated strictly with an increased formation of NK cellor LAK cell/tumor cell conjugate formation. Information on the chemicalspecificity of NK cell and LAK cell interaction with target cells andwith the rhamnogalacturonan was obtained from inhibition studies. Themost efficient inhibitors (100% inhibition at 5 mg/ml) were acetylatedD-mannose and acetylated L-mannonic acid gamma-lactone. Theyspecifically inhibited in a dose-dependent manner: (a) the cytotoxicityof NK cells against K562 cells and the formation of NK cell/K562 cellconjugates; (b) the cytotoxicity of LAK cells against K562 cells andDaudi cells as well as the formation of LAK cell/K562 cell and of LAKcell/Daudi cell conjugates; and (c) the synergistic effects of therhamnogalacturonan in the cytotoxicity assays and the targetcell-conjugate formation assays with NK cells and LAK cells. Theinhibitory effects observed after pretreatment of NK cells or LAK cellswith acetylated mannose were completely reversible, but that obtainedwith acetylated mannonic acid gamma-lactone was only partly reversible,and the degree of reversibility depended on the inhibitor concentrationapplied during pretreatment. Nonacetylated mannose or mannosederivatives up to concentrations of 20 mmol showed no inhibitoryeffects. A mechanistic model representing the interaction of NK cellsand LAK cells with target cells and with rhamnogalacturonan is proposed.

Keyword(s): Medical:tumor-cell-destruction

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