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Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan fromLarix occidentalis

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Abstract

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 fromLarix 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 γ (IFNγ), tumor necrosis factor α, interleukin-1β (IL-1β) and IL-6 but only IFNγ was involved in enhancement of NK cytotoxicity since cytotoxicity enhancement of PBMC and PNAC but not that of monocytes could be blocked when anti-IFNγ 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 fromViscum album extracts since the action of both components was not synergistic but rather competitive.

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  1. Friedrich-Miescher-Laboratorium, Max-Planck-Gesellschaft, Spemannstrasse 37/39, D-7400, Tübingen, Federal Republic of Germany

    Jochen Hauer & F. Alfred Anderer

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  1. Jochen Hauer
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  2. F. Alfred Anderer
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Hauer, J., Anderer, F.A. Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan fromLarix occidentalis . Cancer Immunol Immunother 36, 237–244 (1993). https://doi.org/10.1007/BF01740905

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  • DOI: https://doi.org/10.1007/BF01740905

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