JofLeukocyteBio4-06

Research Abstract

The Effect of PGG-ß-glucan on Neutrophil Chemotaxis in Vivo

Brian W. LeBlanc, Jorge E. Albina and Jonathan S. Reichner1

Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence

The ß-glucans are long-chain polymers of glucose in ß-(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 ß-glucan to increase the chemotactic capacity of human neutrophils. The current study examined an in vivo correlate of that observation by testing the hypothesis that systemic ß-glucan treatment would result in enhanced migration 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 ß-glucan showed a 66 ± 6% and 186 ± 42% increase in wound cell number recovered 6 and 18 h postwounding, respectively. Increased migration did not correlate with increased chemoattractant content 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 ß-glucan without altering normal cellular entry into the wound. Studies also showed a priming effect for chemotaxis and respiratory burst in circulating neutrophils isolated from ß-glucan-treated animals. Heightened neutrophil function took place without cytokine elicitation. Furthermore, ß-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 ß-glucan directly affects the chemotactic capacity of circulating neutrophils through a p38 mitogen-activated protein kinase-dependent mechanism and potentiates antimicrobial host defense.