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Promotion of neutrophil chemotaxis through differential regulation of beta 1 and beta 2 integrins
Journal article   Peer reviewed

Promotion of neutrophil chemotaxis through differential regulation of beta 1 and beta 2 integrins

Mary Beth Harler, Eric Wakshull, Edward J Filardo, Jorge E Albina and Jonathan S Reichner
The Journal of immunology (1950), Vol.162(11), pp.6792-6799
06/01/1999
DOI: 10.4049/jimmunol.162.11.6792
PMID: 10352300

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Abstract

Migration of neutrophils requires sequential adhesive and deadhesive interactions between beta 1 and beta 2 integrins and components of the extracellular matrix. Prompted by reports that describe interaction of soluble beta-glucan with the beta 2 integrin Mac-1, a role for beta-glucan in regulation of integrin-mediated migration was investigated. Neutrophil migration in response to fMLP was assessed using an agarose overlay method with slides precoated with fibronectin (Fn) +/- beta-glucan. On Fn, random migration in excess of directed migration was observed. In contrast, migration on Fn + beta-glucan was directional, with marked diminution of random migration. This conversion of random to directed migration was seen neither when Fn was supplemented with alternative polysaccharides nor when beta-glucan was applied to other components of the extracellular matrix. This effect of beta-glucan was shown to be cation dependent and to be effected by Arg-Gly-Asp-containing peptides consistent with an integrin-mediated event. mAb inhibition studies demonstrate that beta-glucan effects this shift toward directed migration through suppression of migration mediated by Mac-1 and very late Ag 5 and enhancement of very late Ag 3-mediated migration. Adhesion assays suggest that the prochemotactic influence of beta-glucan is due, in part but not entirely, to modulation of PMN adhesion to Fn. In summary, these data support a novel role for beta-glucan in regulation of beta 1- and beta 2-mediated neutrophil migration on Fn.
CD18 Antigens - blood CD18 Antigens - physiology Glucans - immunology CD18 Antigens - immunology Humans Cell Migration Inhibition Integrin beta1 - physiology Cell Movement - immunology Chemotaxis, Leukocyte - drug effects Extracellular Matrix - physiology Binding, Competitive - immunology Integrin beta1 - immunology beta-Glucans Antibodies, Monoclonal - pharmacology Neutrophils - drug effects Neutrophils - immunology Extracellular Matrix Proteins - physiology Glucans - pharmacology Cell Adhesion - immunology Cell Movement - drug effects Fibronectins - physiology Binding Sites, Antibody Chemotaxis, Leukocyte - immunology Integrin beta1 - blood Oligopeptides - pharmacology

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