E-selectin receptors on human leukocytes

Leonardo Nimrichter, Monica M. Burdick, Kazuhiro Aoki, Wouter Laroy, Mark A. Fierro, Sherry A. Hudson, Christopher E. Von Seggern, Robert J. Cotter, Bruce S. Bochner, Michael Tiemeyer, Konstantinos Konstantopoulos, Ronald L. Schnaar

Research output: Contribution to journalArticle

Abstract

Selectins on activated vascular endothelium mediate Inflammation by binding to complementary carbohydrates on circulating neutrophils. The human neutrophil receptor for E-selectln has not been established. We report here that sialylated glycosphingolipids with 5 N-acetyllactosamine (LacNAc, Galß1-4Glc-NAcß1-3) repeats and 2 to 3 fucose residues are major functional E-selectin receptors on human neutrophils. Glycolipids were extracted from 10 10 normal peripheral blood human neutrophils. Individual glycollpid 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 S to 6 LacNAc repeats and 2 to 3 fucose residues were highly potent E-selectin receptors, constituting more than 60% of the E-selectin-blnding activity In the extract. These glycoliplds 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 NeuAcα2-3Gal β1-4GlcNAcβ1-3 [Galβ 1-4(Fucα1-3)Glc-NAcβ1-3] 2[Galβ1-4GlcNAcβ1-3] 2Galβ1-4GlcβCer (and closely related structures) are functional E-selectin receptors.

Original languageEnglish (US)
Pages (from-to)3744-3752
Number of pages9
JournalBlood
Volume112
Issue number9
DOIs
StatePublished - Nov 1 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Nimrichter, L., Burdick, M. M., Aoki, K., Laroy, W., Fierro, M. A., Hudson, S. A., Von Seggern, C. E., Cotter, R. J., Bochner, B. S., Tiemeyer, M., Konstantopoulos, K., & Schnaar, R. L. (2008). E-selectin receptors on human leukocytes. Blood, 112(9), 3744-3752. https://doi.org/10.1182/blood-2008-04-149641