Promotion of Neutrophil Chemotaxis Through Differential Regulation of β1 and β2 Integrins

Abstract

Abstract Migration of neutrophils requires sequential adhesive and deadhesive interactions between β1 and β2 integrins and components of the extracellular matrix. Prompted by reports that describe interaction of soluble β-glucan with the β2 integrin Mac-1, a role for β-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) ± β-glucan. On Fn, random migration in excess of directed migration was observed. In contrast, migration on Fn + β-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 β-glucan was applied to other components of the extracellular matrix. This effect of β-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 β-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 β-glucan is due, in part but not entirely, to modulation of PMN adhesion to Fn. In summary, these data support a novel role for β-glucan in regulation of β1- and β2-mediated neutrophil migration on Fn.