Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan from Larix occidentalis.


Hauer J, Anderer FA




Cancer Immunol Immunother


Cultures of human peripheral blood mononuclear cells (PBMC) as well as cultures of preseparated peripheral non-adherent cells (PNAC) and monocytes showed enhancement of natural killer (NK) cytotoxicity against K562 tumor cells when pretreated with arabinogalactan from Larix occidentalis for 48-72 h. Lack of enhanced responses of PBMC (37% of donors) did not necessarily mean that PNAC and monocyte cultures were also non-responsive to arabinogalactan treatment. Moreover, PBMC, PNAC and monocytes of individual donors could exhibit various responses to arabinogalactan when cultures derived from bleedings after intervals of several months were assayed. Arabinogalactan-mediated enhancement of NK cytotoxicity was not initiated directly but was found to be governed by the cytokine network. Generally, arabinogalactan pretreatment induced an increased release of interferon gamma (IFN gamma), tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta) and IL-6 but only IFN gamma was involved in enhancement of NK cytotoxicity since cytotoxicity enhancement of PBMC and PNAC but not that of monocytes could be blocked when anti-IFN gamma antibodies were present during pretreatment. The presence of anti-IL-2 antibodies completely blocked NK cytotoxicity enhancement of PBMC and only moderately that of PNAC and monocytes. This blocking effect was also observed when no detectable increase of IL-2 release could be recorded. The receptor specificity of arabinogalactan is not well characterized. Initial information obtained from comparative studies indicated that arabinogalactan presumably interacts with a receptor that showed specificity for a NK-cytotoxicity-enhancing oligo-saccharide from Viscum album extracts since the action of both components was not synergistic but rather competitive.