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

Migration of neutrophils requires sequential adhesive and deadhesive intera ctions between beta(1) and beta(2) integrins and components of the extracel lular matrix. Prompted by reports that describe interaction of soluble beta -glucan with the beta(2) integrin Mac-1, a role for beta-glucan in regulati on 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. Th is conversion of random to directed migration was seen neither when Fn was supplemented with alternative polysaccharides nor when beta-glucan was appl ied to other components of the extracellular matrix. This effect of beta-gl ucan was shown to be cation dependent and to be effected by Arg-Gly-Asp-con taining peptides consistent-with an integrin-mediated event. mAb inhibition studies demonstrate that beta-glucan effects this shift toward directed mi gration through suppression of migration mediated by Mac-1 and very late Ag 5 and enhancement of very late Ag 3-mediated migration. Adhesion assays su ggest 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 s upport a novel role for beta-glucan in regulation of beta(1)- and beta(2)-m ediated neutrophil migration on Fn.