E-selectin receptors on human leukocytes
E-selectin receptors on human leukocytes
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DOI：
10.1182/blood-2008-04-149641
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发表时间：
2008-11-01
期刊：
影响因子：
20.3
通讯作者：
Schnaar, Ronald L.
中科院分区：
文献类型：
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作者：
Nimrichter, Leonardo;Burdick, Monica M.;Schnaar, Ronald L.
活化血管内皮上的选择素通过与循环中性粒细胞上的补充碳水化合物结合来介导炎症。 E-选择素的人类中性粒细胞受体尚未确定。我们在此报道，具有 5 个 N-乙酰基乳糖胺（LacNAc、Gal beta 1-4GlcNAc beta 1-3）重复序列和 2 至 3 个岩藻糖残基的唾液酸化鞘糖脂是人中性粒细胞上主要的功能性 E-选择素受体。从10(10)个正常外周血人中性粒细胞中提取糖脂。通过色谱法解析各个糖脂种类，将其吸附为模型膜单层，并且将选择素介导的细胞束缚和流体剪切下的滚动量化为糖脂密度的函数。表达 E-选择素的细胞被束缚并在选定的糖脂上滚动，而表达 P-选择素的细胞则无法相互作用。定量上具有 5 至 6 个 LacNAc 重复序列和 2 至 3 个岩藻糖残基的少量末端唾液酸化鞘糖脂是高效的 E-选择素受体，构成提取物中 60% 以上的 E-选择素结合活性。这些糖脂在人血液中性粒细胞上的表达密度超过支持 E-选择素介导的束缚和滚动所需的密度。阻断培养的人中性粒细胞中鞘糖脂的生物合成会减少 E-选择素的粘附，但不会减少 P选择素的粘附。数据支持以下结论：对于人中性粒细胞，糖鞘脂 NeuAc α 2-3Gal beta 1-4GlcNAc beta 1-3 [Gal beta 1-4 (Fuc alpha 1-3)GlcNAc beta 1-3](2) [Gal beta 1-4GlcNAc beta 1-3](2)Gal beta 1-4Glc beta er（以及密切相关的结构）具有功能性E-选择素受体。 （血。2008；112：3744-3752）
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, Gal beta 1-4GlcNAc beta 1-3) 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 Pselectin, adhesion. The data support the conclusion that on human neutrophils the glycosphingolipid NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-3 [Gal beta 1-4 (Fuc alpha 1-3)GlcNAc beta 1-3](2) [Gal beta 1-4GlcNAc beta 1-3](2)Gal beta 1-4Glc beta er (and closely related structures) are functional E-selectin receptors. (Blood. 2008; 112:3744-3752)