Effects of beta-glucan on leukocyte function

Although the innate immune system has been studied for a number of years, a well-defined pharmacological agent able to beneficially prime leukocyte microbicidal functions has yet to be developed. This is because the signaling events required for leukocyte priming result in the overproduction of pro-inflammatory cytokines at insupportable levels. The beta-glucans are a class of glucose polymers that comprise the cell wall of yeast and fungi and have been shown to stimulate the innate immune system. Using a non-phlogistic preparation of beta-glucan as a priming agent, studies contained herein demonstrate the simultaneous enhancement of microbicidal activities along with inhibition of pro-inflammatory cytokine stimulation. Studies were designed to delineate the mechanism for the enhanced migration and decreased cytokine production. When administered in vivo, beta-glucan showed an increase in leukocyte migration into a wound at 6 and 18 hours post-wounding, without increased chemoattractant content of wound fluid. beta-glucan treatment failed to effect neutrophil-induced loss of endothelial barrier function, or changes in neutrophil adhesion to endothelial cells. Systemic administration of SB203580, a specific p38 MAPK inhibitor, abrogated the enhanced migration by beta-glucan without altering normal cellular entry into the wound. beta-glucan treatment primed for chemotaxis and respiratory burst activity in circulating neutrophils isolated from beta-glucan-treated animals. Heightened neutrophil function took place without cytokine elicitation. Furthermore, beta-glucan treatment demonstrated increased neutrophil response to, and decreased bacterial load in the broncho-alveolar lavage fluid of E. coli pneumonic animals.;beta-glucan pretreatment of leukocytes resulted in the decrease in an NF-kappaB-mediated, LPS-stimulated pro-inflammatory cytokine production. Using a cell line deficient in CD11b/CD18 and blocking antibodies for Dectin-1 studies herein determined that neither CR3 nor Dectin-1 function in this observed beta-glucan effect. However, antibody blocking of the glycosphingolipid lactosylceramide (CDw17) significantly limited the suppressive effect of beta-glucan on stimulant induced cytokine production. Taken together, beta-glucan is an immune modulator capable of priming leukocyte functions without stimulating pro-inflammatory cytokines.