Leukocyte-borne α(1,3)-fucose is a negative regulator of β2-integrin-dependent recruitment in lung inflammation

Leukocyte recruitment in inflammation is a multistep, sequential cascade where the initial step is the selectindependent tethering, followed by the formation of firmer integrin-mediated adhesive forces leading to extravasation. The alpha(1,3)-fucose-containing sialyl-Lewis X (sLe(X)) is the archetypical ligand on leukocyte surfaces mediating selectin interactions. Canonically, disruption of alpha(1,3)fucose formation ablates selectin-mediated adhesion, dramatically reducing trafficking. We report a paradoxical response to alpha(1,3)-fucose deficiency in which the loss exacerbated rather than attenuated leukocyte recruitment in a murine model of acute airway inflammation. The architecture of the capillary-dominated vasculature in the lung minimized the importance of the selectin dependent step, and we observed that alpha(1,3)-fucose deficiency augmented CXCR2-mediated Rap1-GTP signaling to enhance the beta(2)-integrin-ICAM-1-binding axis. The data disclose a previously unknown function for alpha(1,3)-fucose, in which this structure negatively regulates the integrin activation step in leukocyte recruitment.