Modulation of the β2-Integrin Axis in Inflammatory Cell Trafficking By Fucosylated Ligands

Leukocyte trafficking to a site of inflammation, in which selectin-mediated recruitment is the well-established initial step in mouse and humans, requires α1,3-fucosylated carbohydrates as canonical selectin ligands. Disrupting these ligands mitigates leukocyte recruitment, and this pathway presents a choice target in managing inflammatory conditions. Here we report that fucose can act paradoxically in cell recruitment to select sites of inflammation. α1,3-Fucose deficient neutrophils lacking the fucosyltransferases Fut4 and Fut7 have severely impaired recruitment in the well-established selectin dependent acute peritonitis. By contrast they are preferentially recruited to inflamed airways, because α1,3-fucose deficiency augments CXCR2 mediated Rap1-GTP signaling and enhances the β2 integrin - ICAM-1 axis to promote neutrophil recruitment. Recognition of this newly identified role for α1,3-fucoslated carbohydrates in modulating the integrin axis of inflammatory cell recruitment illuminates the unique pathophysiology of the airway and new insights into therapeutic anti-inflammatory approaches.