Chemical specificity of effector cell/tumor cell bridging by a VISCUM ALBUM rhamnogalacturonan enhancing cytotoxicity of human NK cells
Journal/Book: Immunopharmacology 19 (1), 69-77. 1990;
Abstract: The component in Viscum album extract Iscador-M enhancing the NKcytotoxicity of human CD56+CD3- NK cells (87-95% enrichment) incocultures with K562 tumor cells and increasing the formation of NKcell/tumor cell conjugates was identified as a rhamnogalacturonan. Bothactivities were abolished by treatment of V. album extract withpoly-alpha-D-galacturonidase and alpha-rhamnosidase and both activitieswere inhibited in the presence of galacturonic acid and acetylatedrhamnose (6-deoxymannose). Inhibition was also observed in the presenceof structurally related derivatives such as acetylated mannose oracetylated mannonic acid gamma-lactone, the latter exhibiting a5-10-fold higher inhibitory potential. The rapid formation of NKcell/tumor cell conjugates in the presence of V. album extract was basedon the bridging of NK cells with tumor cells by rhamnogalacturonan.Using a specifically adapted agglutination assay, the saccharideresidues of the rhamnogalacturonan interacting with NK cells and tumorcells could be identified by the formation of homologous cell conjugatesinduced by acetylated rhamnose or acetylated mannose conjugated todextran and by polygalacturonic acid: terminal acetylated rhamnose oracetylated mannose bound only to NK cells in a dose-dependent manner butnot to K562 tumor cells, and terminal galacturonic acid only to K562tumor cells but not to NK cells. This type of bridging represents anovel mechanism of enhancement of NK cytotoxicity. Author.