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

cited authors

  • Buffone, A; Nasirikenari, M; Manhardt, CT; Lugade, A; Bogner, PN; Sackstein, R; Thanavala, Y; Neelamegham, S; Lau, JTY

fiu authors

abstract

  • 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 α(1,3)-fucose-containing sialyl-Lewis X (sLeX) is the archetypical ligand on leukocyte surfaces mediating selectin interactions. Canonically, disruption of α(1,3)- fucose formation ablates selectin-mediated adhesion, dramatically reducing trafficking. We report a paradoxical response to α(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 α(1,3)-fucose deficiency augmented CXCR2-mediated Rap1-GTP signaling to enhance the β2-integrin-ICAM-1-binding axis. The data disclose a previously unknown function for α(1,3)-fucose, in which this structure negatively regulates the integrin activation step in leukocyte recruitment.

publication date

  • February 1, 2017

Digital Object Identifier (DOI)

start page

  • 459

end page

  • 470

volume

  • 101

issue

  • 2