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

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 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.

Induction of secretory and tumoricidal activities in peritoneal macrophages activated by an acidic heteropolysaccharide (ARAGAL) from the gum of Anadenanthera colubrina (Angico branco)

“…Arabinogalactans are found in several microbial systems and many plants, mostly in a glycopeptide form, bound to threonine, proline or serine and then to a peptide chain (arabinogalactan protein (AGP)) [34]. There is much evidence that arabinogalactans can interfere in the immune response [29,31], examples being those isolated from Echinacea purpurea, Baptisia tinctoria, Thuja occidentalis [29], Angelica acutiloba [35], and Curcuma longa [30]. Saima et al [27], have isolated an anti-tumor acidic polysaccharide from the fruit of Feronia limonia (Linn.).…”

“…A class that has been receiving attention is the arabinogalactan [28][29][30][31][32][33][34], which consists of heavily branched highmolecular weight polysaccharides (mw 10,000-120,000) [31]. Arabinogalactans are found in several microbial systems and many plants, mostly in a glycopeptide form, bound to threonine, proline or serine and then to a peptide chain (arabinogalactan protein (AGP)) [34].…”

Larch arabinogalactan effects on reducing incidence of upper respiratory infections

“…Indeed, our data are in line with in vitro and animal studies that showed various immunomodulating effects of arabinogalactan on markers of the innate as well as adaptive immunity. Hence, in response to arabinogalactan, human peripheral blood mononuclear cells (PBMC) and their subpopulations have been shown to release pro-inflammatory cytokines which stimulated NK cytotoxicity 11 . Moreover, larch arabinogalactan activated lymphocytes and macrophages in vitro which provokes a variety of cellular response including enhanced phagocytosis, oxidative burst and the modulation of cytokine production 9 .…”

“…Arabinogalactan from larch was demonstrated to stimulate the innate immunity by increasing the NK cell cytotoxicity and the phagocytic capacity of macrophages and monocytes mediated by pro-inflammatory cytokines [9][10][11][12] . Udani et al 13 suggested that arabinogalactan acts in a more specific manner on the adaptive immunity, as shown in the increase in antibody response to the pneumonia vaccine.…”

Extracts of Larix Leptolepis effectively augments the generation of tumor antigen-specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner

“…These results suggest that some complex of Galactose, Arabinose and/or Gulucose might be novel ligands for TLR2 or TLR4. Indeed, arabinogalactan, lipoarabinomannan and galactomannan were reported as stimulator of DCs [49][50][51]. Previously, it is reported that arabinogalactan have an adjuvant activity for human PBMC.…”