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Blood. 2008 Nov 1;112(9):3744-52. doi: 10.1182/blood-2008-04-149641. Epub 2008 Jun 25.

E-selectin receptors on human leukocytes.

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  • 1Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.

Abstract

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, Galbeta1-4GlcNAcbeta1-3) 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 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 NeuAcalpha2-3Galbeta1-4GlcNAcbeta1-3[Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3](2)[Galbeta1-4GlcNAcbeta1-3](2)Galbeta1-4GlcbetaCer (and closely related structures) are functional E-selectin receptors.

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PMID:
18579791
[PubMed - indexed for MEDLINE]
PMCID:
PMC2572800
Free PMC Article
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