The effect of PGG-beta-glucan on neutrophil chemotaxis in vivo.
The beta-glucans are long-chain polymers of glucose in beta-(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 beta-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 beta-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 beta-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 beta-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 beta-glucan-treated animals. Heightened neutrophil function took place without cytokine elicitation. Furthermore, beta-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 beta-glucan directly affects the chemotactic capacity of circulating neutrophils through a p38 mitogen-activated protein kinase-dependent mechanism and potentiates antimicrobial host defense.
LeBlanc
Brian W
BW
Department of Surgery, Rhode Island Hospital, NAB 219, 593 Eddy Street, Providence, RI 02903, USA.
Albina
Jorge E
JE
Reichner
Jonathan S
JS
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011462:Prostaglandins G; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology; D047071:beta-Glucans / Q000008:administration & dosage* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D007093:Imidazoles; D011462:Prostaglandins G; D011725:Pyridines; D047071:beta-Glucans; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580