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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3744-3752. Prepublished online as a Blood First Edition Paper on June 25, 2008; DOI 10.1182/blood-2008-04-149641. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-04-149641v1 112/9/3744    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 Citing Articles via Google Scholar Google Scholar Articles by Nimrichter, L. Articles by Schnaar, R. L. Search for Related Content PubMed PubMed Citation Articles by Nimrichter, L. Articles by Schnaar, R. L. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY E-selectin receptors on human leukocytes Leonardo Nimrichter1,2, Monica M. Burdick3, Kazuhiro Aoki4, Wouter Laroy1, Mark A. Fierro1, Sherry A. Hudson5, Christopher E. Von Seggern1, Robert J. Cotter1, Bruce S. Bochner5, Michael Tiemeyer4, Konstantinos Konstantopoulos3, and Ronald L. Schnaar1 1 Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, MD; 2 Instituto de Microbiologia Prof Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 3 Department of Chemical & Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD; 4 Department of Biochemistry and Molecular Biology and The Complex Carbohydrate Research Center, University of Georgia, Athens; and 5 Department of Medicine, Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore, MD Selectins on activated vascular endothelium mediate inflammation by binding to complementary carbohydrates on circulating neutrophils. The human neutrophil receptor for E-selectin has not been established. We report here that sialylated glycosphingolipids with 5 N-acetyllactosamine (LacNAc, Galβ1-4GlcNAcβ1-3) repeats and 2 to 3 fucose residues are major functional E-selectin receptors on human neutrophils. Glycolipids were extracted from 1010 normal peripheral blood human neutrophils. Individual glycolipid species were resolved by chromatography, adsorbed as model membrane monolayers and selectin-mediated cell tethering and rolling under fluid shear was quantified as a function of glycolipid density. E-selectin–expressing cells tethered and rolled on selected glycolipids, whereas P-selectin–expressing cells failed to interact. Quantitatively minor terminally sialylated glycosphingolipids with 5 to 6 LacNAc repeats and 2 to 3 fucose residues were highly potent E-selectin receptors, constituting more than 60% of the E-selectin–binding activity in the extract. These glycolipids are expressed on human blood neutrophils at densities exceeding those required to support E-selectin–mediated tethering and rolling. Blocking glycosphingolipid biosynthesis in cultured human neutrophils diminished E-selectin, but not P-selectin, adhesion. The data support the conclusion that on human neutrophils the glycosphingolipid NeuAc2-3Galβ1-4GlcNAcβ1-3[Galβ1-4(Fuc1-3)GlcNAcβ1-3]2[Galβ1-4GlcNAcβ1-3]2Galβ1-4GlcβCer (and closely related structures) are functional E-selectin receptors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: E-selectin prefers fatty-sweet receptors on rolling neutrophils Scott I. Simon Blood 2008 112: 3537. [Full Text] [PDF]

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