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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Thanavala, Yasmin¹  Bogner, Paul N.¹  Lau, Joseph T. Y.¹  Manhardt, Charles T.¹  Sackstein, Robert⁷  Lugade, Amit⁸  Nasirikenari, Mehrab⁸  Neelamegham, Sriram⁹ 

[1] Women’and..Program of Excellence in Glycosciences, Harvard Medical School, Boston, Massachusetts, USA;..Department of Medicine, Brigham &Department of Chemical and Biological Engineering, State University of New York at Buffalo, Buffalo, New York, USA;Department of Dermatology Brigham &Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA;Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York, USA;Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York, USA;s Hospital, Harvard Medical School, Boston, Massachusetts, USA

关键词: fucosyltransferase;    neutrophil;    ICAM‐;    1;    CXCR2;    NTHI;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Leukocyte recruitment in inflammation is a multistep, sequential cascade where the initial step is the selectin-dependent tethering, followed by the formation of firmer integrin-mediated adhesive forces leading to extravasation. The α(1,3)-fucose-containing sialyl-Lewis X (sLe^X) 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.

【 授权许可】

CC BY