Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan from LARIX OCCIDENTALIS

Journal/Book: Cancer-Immunol-Immunother 36 (4), 237-44. 1993;

Abstract: Cultures of human peripheral blood mononuclear cells (PBMC) as well ascultures of preseparated peripheral non-adherent cells (PNAC) andmonocytes showed enhancement of natural killer (NK) cytotoxicity againstK562 tumor cells when pretreated with arabinogalactan from Larixoccidentalis for 48-72 h. Lack of enhanced responses of PBMC (37% ofdonors) did not necessarily mean that PNAC and monocyte cultures werealso non-responsive to arabinogalactan treatment. Moreover, PBMC, PNACand monocytes of individual donors could exhibit various responses toarabinogalactan when cultures derived from bleedings after intervals ofseveral months were assayed. Arabinogalactan-mediated enhancement of NKcytotoxicity was not initiated directly but was found to be governed bythe cytokine network. Generally, arabinogalactan pretreatment induced anincreased release of interferon gamma (IFN gamma), tumor necrosis factoralpha, interleukin-1 beta (IL-1 beta) and IL-6 but only IFN gamma wasinvolved in enhancement of NK cytotoxicity since cytotoxicityenhancement of PBMC and PNAC but not that of monocytes could be blockedwhen anti-IFN gamma antibodies were present during pretreatment. Thepresence of anti-IL-2 antibodies completely blocked NK cytotoxicityenhancement of PBMC and only moderately that of PNAC and monocytes. Thisblocking effect was also observed when no detectable increase of IL-2release could be recorded. The receptor specificity of arabinogalactanis not well characterized. Initial information obtained from comparativestudies indicated that arabinogalactan presumably interacts with areceptor that showed specificity for a NK-cytotoxicity-enhancingoligo-saccharide from Viscum album extracts since the action of bothcomponents was not synergistic but rather competitive. Author.

Keyword(s): CYTOKINES/ ME (metabolism)

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