The effect of PGG--glucan on neutrophil chemotaxis in vivo

Abstract: The -glucans are long-chain polymers of glucose in -(1,3)(1,6) linkages, which comprise the fungal cell wall and stimulate cells of the innate immune system. Previous in vitro studies have shown the ability of -glucan to increase the che-motactic capacity of human neutrophils. The cur-rent study examined an in vivo correlate of that observation by testing the hypothesis that systemic -glucan treatment would result in enhanced mi-gration of neutrophils into a site of inflammation and improve antimicrobial function. A model of acute inflammation was used in which polyvinyl alcohol sponges were implanted subcutaneously into the dorsum of rats. Animals treated with -glu-can showed a 66 6 % and 186 42 % increase in wound cell number recovered 6 and 18 h post-wounding, respectively. Increased migration did not correlate with increased chemoattractant con-tent of wound fluid, alterations in neutrophil-induced loss of endothelial barrier function, or changes in neutrophil adhesion to endothelial cells. Systemic administration of SB203580 abrogated the enhanced migration by -glucan without alter-ing normal cellular entry into the wound. Studies also showed a priming effect for chemotaxis and respiratory burst in circulating neutrophils isolated from -glucan-treated animals. Heightened neu-trophil function took place without cytokine elici-tation. Furthermore, -glucan treatment resulted in a 169 28 % increase in neutrophil number and a 60 9 % decrease in bacterial load in the bronchoalveolar lavage fluid of Escherichia coli pneumonic animals. Taken together, these findings demonstrate that -glucan directly affects the che-motactic capacity of circulating neutrophils through a p38 mitogen-activated protein kinase-dependent mechanism and potentiates antimicro-bial host defense. J. Leukoc. Biol. 79: 667–675