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.

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Inhibition of specific cytotoxicity of highly purified (> 95%) human CD56+ NK and LAK cells against K562 tumour cells was studied with various sugar acetates. Maximum inhibitory specificity was obtained with 60%-deacetylated penta-acetates of mannose, galactose, glucose, or 80%-deacetylated penta-O-acetate of N-acetyl neuraminic acid. The inhibition was strictly dosedependent and 100% inhibition was achieved in the concentration range of 500-1000 nmoles/ml with all four sugar acetate samples. Enhancement of specific cytotoxicity in the presence of rhamnogalacturonan (RG; 500 ng/ml), acting as a bridging molecule, was also inhibited in a dose-dependent manner with the same inhibitory specificity and within the same concentration range indicating involvement of the same number of sugar acetate-specific receptors. Moreover, formation of lytic CD56+ effector cell/tumour cell (E/T) conjugates was equally well inhibited whereas formation of total E/T conjugates was only partially inhibited (NK: 44-73%; LAK: 46-50%). E/T conjugate formation in the presence of RG was enhanced. Inhibition of the enhancement of formation of lytic E/T conjugates in the presence of RG was again completely accomplished with the same inhibitory specificity and within the same concentration ranges as recorded for E/T conjugate formation in the absence of RG. However, inhibition of total E/T conjugate formation was again only partially achieved at the given concentrations. The data support the assumption of an NK cell receptor with specificity for acetylated carbohydrate moieties on target cells or on bridging molecules such as RG.

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