PGG-Glucan, a soluble beta-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-kappa B-like factor in human PMN: Evidence for a glycosphingolipid beta-(1,3)-glucan receptor

PGG-Glucan, a soluble beta-(1,6)-branched beta-(1,5)-linked glucose homopol ymer derived from the cell wall of the yeast Saccharomyces cerevisiae, is a n immunomodulator which enhances leukocyte anti-infective activity and enha nces myeloid and megakaryocyte progenitor proliferation. Incubation of huma n whole blood with PGG-Glucan significantly enhanced the oxidative burst re sponse of subsequently isolated blood leukocytes to both soluble and partic ulate activators in a dose-dependent manner, and increased leukocyte microb icidal activity. No evidence for inflammatory cytokine production was obtai ned under these conditions. Electrophoretic mobility shift assays demonstra ted that PGG-Glucan induced the activation of an NF-kappa B-like nuclear tr anscription factor in purified human neutrophils. The binding of H-3-PGG-Gl ucan to human leukocyte membranes was specific, concentration-dependent, sa turable, and high affinity (K-d similar to 6 nM). A monoclonal antibody spe cific to the glycosphingolipid lactosylceramide was able to inhibit activat ion of the NF-kappa B-like factor by PGG-Glucan, and ligand binding data, i ncluding polysaccharide specificity, suggested that the PGG-Glucan binding moiety was lactosylceramide. These results indicate that PGG-Glucan enhance s neutrophil anti-microbial functions and that interaction between this bet a-glucan and human neutrophils is mediated by the glycosphingolipid lactosy lceramide present at the cell surface. (C) 1999 Published by Elsevier Scien ce B.V. All rights reserved.