Modification of Immunostimulating Activities of Grifolan by the Treatment with (1—.3)-p-D-Glucanase
Isao NONO, Naohito OHNO,* Masumi OHSAWA, Shozo OIKAWA,** and Toshiro YADOMAE*
Tokyo College of Pharmacy, * Horinouchi, Hachioji, Tokyo, 192-03, Japan and Nippon Beet Sugar Mfg., Co., Ltd., ** Chuo-ku, Tokyo, 104, Japan
We have developed a method to control the effective time period of (1->3)-β-D-glucan in vivo by using (1->3)-β-D-glucanase and found that grifolan LE (GRN), from maitake ) , a (1->3)-β-D-glucan, administered intraperitoneally to the host required more than 2 d to exert antitumor activity. During these two days many immunological changes were induced, such as increasing the number of peritoneal exudated cells (PEC), augmentation of production of interleukin 1 (IL-1), acid phosphatase and phagocytic capacity of adherent cells in PEC. In addition, there was increased carbon clearance activity in vivo, augmentation of responsiveness of splenocytes to mitogens such as concanavalin A and lipopolysaccharide (LPS) and production of ceruloplasmin. When (1->3) β-D-glucanase was injected 1 d after GRN administration, IL-1 productivity and responsiveness to LPS were significantly reduced, but lysosomal enzyme activity and phagocytosis of macrophage and production of ceruloplasmin were similar to those not treated with glucanase. These facts indicate that the induction of the activities of the former group requires longer contact of host cells with the glucan, and the latter group requires a shorter period to achieve fully active stages.