Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 101, Issue 2, Pages 459-470Publisher
WILEY
DOI: 10.1189/jlb.3A0516-215RR
Keywords
fucosyltransferase; neutrophil; ICAM-1; CXCR2; NTHI
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Funding
- U. S. National Institutes of Health (NIH), National Heart, Lung, and Blood Institute [HL63014, HL103411]
- Program of Excellence in Glycosciences [HL107146]
- NIH National Cancer Institute Cancer Center Support Grant [CA15056]
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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.
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