The effect of PGG‐β‐glucan on neutrophil chemotaxis in vivo

The β‐glucans are long‐chain polymers of glucose in β‐(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 β‐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 β‐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 β‐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 β‐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 β‐glucan‐treated animals. Heightened neutrophil function took place without cytokine elicitation. Furthermore, β‐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 β‐glucan directly affects the chemotactic capacity of circulating neutrophils through a p38 mitogen‐activated protein kinase‐dependent mechanism and potentiates antimicrobial host defense.