Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component from viscum album extract

Viscum album extracts (Helixor) were investigated for their potency to influence natural killer cell (NK) cytotoxicity of human peripheral blood mononuclear cells (PBMC) in vitro. The samples investigated were unable to enhance NK cytotoxicity in PBMC/tumor cell co-cultures by direct short-term mediation but NK cytotoxicity of human PBMC was strongly stimulated when PBMC were pre-incubated for 72 h with a partly purified fraction (HM-BP) derived from extracts of V. album mali. Stimulation of NK cytotoxicity was not dependent from age and sex of PBMC donors and was directed against highly as well as moderately NK-sensitive human tumor cells. The responding effector cells were identified as monocytes/macrophages and stimulation of the NK cytotoxicity of these cells was not based on increased proliferation. The active component in the HM-BP fraction has a molecular weight of about 1000 Da or smaller and correlates with the structural criteria of an oligosaccharide. The activity was completely abrogated when the active fraction was treated with endoglycosidase F or alpha-glucosidase. Partial inactivation was observed after treatment with endoglycosidase D or hemicellulase. Moreover, the active fraction induced a reduction in tumor take incidence and tumor development in mice when applied before and after tumor challenge.