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MODULATION OF CYTOKINE AND IMMUNOGLOBLIN A RELEASE BY BETA-(1,3-1,6)-GLUCAN FROM AUREOBASIDIUM PULLULANS STRAIN 1A1
Takahiro Suzuki1, Akira Hosono2, Satoshi Hachimura3, Toshio Suzuki1, and Shuichi Kaminogawa 2
1Research Laboratories, DAISO CO., LTD., Otakasu-cho, Amagasaki-shi, Hyogo, 660-0842, Japan. Department of Food Science and Technology, Nihon University. Department of Applied Biological Chemistry, The University of Tokyo
Abstract: Beta-glucan, derived from mushroom or yeast extracts, is well known for its various immunopharmacological effects such as anti-microbial properties and anti-tumor activities for host defense. We isolated P-glucans (DS-PG), secreted by the fungus body, from the culture medium of Aureobasidium pullulans strain 1A1. DS-PG form soluble microparticles and we prepared DS-PG to 85-95% purity. The structure of DS-PG is based on a backbone of P-(1,3)-linked P-D-glucopyranosyl units, with P-(1,6) linked side-chains of varying distribution. Their molecular weight range is 50,000-300,000, with the average estimated to be 100,000. In this study, we investigated the immunomodulatory effects of DS-PG, especially its in vitro and in vivo effects on the intestinal immune system. Peyer's patches (PP) cells from BALB/cA mice were cultured with DS-PG (0~200^g/ml) and IgA and cytokine levels in culture supernatant measured by ELISA. The addition of DS-PG induced IgA production in a dose-dependent manner. Both the levels of interleukin-5 (IL-5) and interleukin-6 (IL-6), cytokines known to enhance IgA production, were also elevated. Oral administration of DS-PG (400^g/mouse/day) for 7 consecutive days induced IgA production by PP cells. These results demonstrate that DS-PG acts on the gut immune system and increase IgA production that is vitally important for defense against infection.
Key words: ß-(1,3-1,6)-glucan; Aureobasidium pullulans; immunomodulation
Many kinds of fungi, yeasts and plants have immunomodulatory effects such as anti-microbial and anti-tumor activities important for host defense. These have been used clinically, as in the cases of lentinan (from Lentinus edodes), shyzophillan (from Schizophyllum commune) and Krestin (from Coriolus versicolor) for example (Adachi et al., 1994). Schizophyllan shows anti-tumor activity against sarcoma180, sarcoma37 etc (Hobbs, 1995). Lentinan significantly increased macrophage cytotoxicity in vivo when injected subcutaneously or intraperitoneally (Hamuro et al., 1980, Ladânyi et al., 1993). P-glucan is known to be the major active constituent responsible for eliciting the immune responses of these molecules. It is an indigestive polysaccharide in humans. In light of these facts, it is speculated that P-glucans may modulate mucosal immunity in the intestinal tract.
Recent analysis of the response of leukocytes to P-glucan has shown that the integrin CR3 or dectin-1 receptor is required for its binding to cells (Xia et al., 1999, Brown et al., 2001, Thornton et al., 1996). P-glucans are known to act as immunostimulants, enhancing the activities of leukocytes, especially macrophages and natural killer cells (Konopski et al., 1991; Onderdonk et al., 1992). However, the mechanism of their immunomodulatory activities is not completely understood. The various physiological functions of different P-glucans have not been well clarified because of differences in their origin, the bonding pattern, the molecular weight and/or the size of the particles that contain the P-glucans (Janelle et al., 1999). In addition, the purification of P-glucan is difficult and few studies have investigated immune responses to purified P-glucan.
In this study, we isolated the original and purified P-glucan (DS-PG) from the culture of Aureobasidium pullulans strain 1A1 by fermentation methods, and determined the possibility to supplying them in large amounts (through Daiso, Osaka, Japan). DS-PG is a soluble microparticle glucan of low-molecular mass and with 50-80% (P-1,6/P-1,3) branches. Additionally, we prepared DS-PG to around 85-95% purity. We investigated cellular immune responses to DS-PG, including cytokine and immunoglobulin A production in the mouse intestinal tract immune system.
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