期刊
BLOOD
卷 112, 期 5, 页码 2035-2045出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-04-149468
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类别
资金
- National Institutes of Health [HL 34363, HL 085607, RR 018758]
In inflamed venules, leukocytes use P-selectin glycoprotein ligand-1 (PSGL-1) to roll on P-selectin and E-selectin and to activate integrin alpha L beta 2 (lymphocyte function-associated antigen-1, LFA-1) to slow rolling on intercellular adhesion molecule-1 (ICAM-1). Studies in cell lines have suggested that PSGL-1 requires its cytoplasmic domain to localize in membrane domains, to support rolling on P-selectin, and to signal through spleen tyrosine kinase (Syk). We generated Delta CD mice that express PSGL-1 without the cytoplasmic domain. Unexpectedly, neutrophils from these mice localized PSGL-1 normally in microvilli, uropods, and lipid rafts. Delta CD neutrophils expressed less PSGL-1 on their surfaces because of inefficient export from the endoplasmic reticulum. Limited digestion of wild-type neutrophils with O-sialoglycoprotein endopeptidase was used to reduce the PSGL-1 density to that on Delta CD neutrophils. At matched PSGL-1 densities, both Delta CD and wild-type neutrophils rolled similarly on P-selectin. However, Delta CD neutrophils rolling on P-selectin did not trigger Syk-dependent activation of LFA-1 to slow rolling on ICAM-1. These data demonstrate that the PSGL-1 cytoplasmic domain is dispensable for leukocyte rolling on P-selectin but is essential to activate beta 2 integrins to slow rolling on ICAM-1.
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