Passive transfer of poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose glucan protection against lethal infection in an animal model of intra-abdominal sepsis

Abstract

Previous studies have established the efficacy of soluble polymers of poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose (PGG) glucan, a biological-response modifier, in protecting against mortality associated with experimentally induced peritonitis in a rat model. PGG glucan-treated animals showed increases in total leukocyte counts and enhanced bacterial clearance from blood. To further explore the mechanisms) by which this agent confers protection, studies were performed to examine whether protection could be transferred from PGG glucan-treated animals to naive recipients via spleen cells (SC), SC lysates, or serum. Passive-transfer experiments indicated that the responsible factor(s) was transferable by whole SC and SC lysates, as well as by peripheral leukocytes or serum from animals treated with PGG glucan. The transferable factor(s) was resistant to pronase and trypsin digestion, was heat stable at 56 or 80 degrees C, and was not removed by NH4SO4 precipitation. The protective effect of PGG glucan was abrogated by treatment with indomethacin, a potent inhibitor of prostaglandin synthesis. Administration of a purified prostaglandin extract from the sera of PGG glucan-treated animals protected against mortality in the peritonitis model. Furthermore, treatment of rats with exogenous synthetic prostaglandin E2 also conferred protection against mortality. These results suggest that the protective effect exhibited by PGG glucan in the rat peritonitis model is mediated, at least in part, by prostaglandins.