Promotion of neutrophil chemotaxis through differential regulation of beta 1 and beta 2 integrins.
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.
Harler
M B
MB
Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Brown University School of Medicine, Providence 02903, USA.
Wakshull
E
E
Filardo
E J
EJ
Albina
J E
JE
Reichner
J S
JS
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D018821:CD18 Antigens / Q000097:blood / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D005936:Glucans / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D019012:Integrin beta1 / Q000097:blood / Q000276:immunology / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D047071:beta-Glucans
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005936:Glucans; D019012:Integrin beta1; D009842:Oligopeptides; D047071:beta-Glucans; C047981:arginyl-glycyl-aspartic acid; C033363:beta-1,3-glucan