SEARCH:   Advanced

Blood, 1 September 2008, Vol. 112, No. 5, pp. 2035-2045. Prepublished online as a Blood First Edition Paper on June 11, 2008; DOI 10.1182/blood-2008-04-149468. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-149468v1 112/5/2035    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Miner, J. J. Articles by McEver, R. P. PubMed PubMed Citation Articles by Miner, J. J. Articles by McEver, R. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow Jonathan J. Miner*,1,2, Lijun Xia*,1,2, Tadayuki Yago1, János Kappelmayer1, Zhenghui Liu1, Arkadiusz G. Klopocki1, Bojing Shao1, J. Michael McDaniel1, Hendra Setiadi1, David W. Schmidtke3,4, and Rodger P. McEver1,2 1 Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation and 2 Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City; 3 University of Oklahoma Bioengineering Center and 4 School of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman In inflamed venules, leukocytes use P-selectin glycoprotein ligand-1 (PSGL-1) to roll on P-selectin and E-selectin and to activate integrin Lβ2 (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 "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. 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 CD neutrophils. At matched PSGL-1 densities, both CD and wild-type neutrophils rolled similarly on P-selectin. However, 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 β2 integrins to slow rolling on ICAM-1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020