THE HNK-1 REACTIVE SULFOGLUCURONYL GLYCOLIPIDS ARE LIGANDS FOR L-SELECTIN AND P-SELECTIN BUT NOT E-SELECTIN
THE HNK-1 REACTIVE SULFOGLUCURONYL GLYCOLIPIDS ARE LIGANDS FOR L-SELECTIN AND P-SELECTIN BUT NOT E-SELECTIN
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DOI：
10.1073/pnas.90.4.1359
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发表时间：
1993-02-15
影响因子：
11.1
通讯作者：
SCHNAAR, RL
中科院分区：
文献类型：
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作者：
NEEDHAM, LK;SCHNAAR, RL
E-选择素、L-选择素和P-选择素是相关的细胞粘附分子，其通过其凝集素结构域结合唾液酸刘易斯x和相关的碳水化合物决定簇。报告表明，硫酸化糖脂和多糖也结合选择素。为了扩展这些发现，我们比较了选择素-IgG嵌合体与固定化硫酸化和唾液酸化鞘糖脂的结合。E-、L-和P-选择素嵌合体均与吸附有2，3-唾液酸刘易斯x糖脂或硫苷脂（半乳糖神经酰胺I3-硫酸盐）的表面结合，但不与吸附有对照硫酸化脂质（硫酸十八烷基酯、硫酸鞘氨醇）的表面结合。值得注意的是，L-和P-选择素嵌合体而不是E-选择素嵌合体结合到吸附有磺基葡糖醛酸鞘糖脂（SGNL脂质;例如，IV 3葡萄糖醛酸基新乳四糖神经酰胺V 3-硫酸盐）。据报道，这些不寻常的脂质是与副蛋白血症相关的神经病患者产生的单克隆IgM抗体的抗原决定簇，并与小鼠单克隆抗体HNK-1反应。适当的抗选择素抗体特异性抑制L-和P-选择素嵌合体与SGNL脂质的结合。虽然所有三种选择素嵌合体与唾液酸刘易斯x的结合被钙的去除阻断，但与SGNL脂质的结合仅被EDTA适度降低。化学修饰的SGNL脂质保留了对L-和P-选择素嵌合体的结合活性，而葡萄糖醛酸的甲酯化消除了结合。我们得出结论，SGNL脂质，不像唾液酸刘易斯x和硫苷脂，选择性地支持L-和P-选择素，但不支持E-选择素嵌合体结合。脑微血管内皮（和其他内皮）上SGNL脂质的存在可能涉及这些分子在白细胞运输到神经系统和其他地方。
E-selectin, L-selectin, and P-selectin are related cell adhesion molecules that bind via their lectin domains to sialyl Lewis x and related carbohydrate determinants. Reports have indicated that sulfated glycolipids and polysaccharides also bind selectins. To extend these findings, we compared binding of selectin-IgG chimeras to immobilized sulfated and sialylated glycosphingolipids. E-, L-, and P-selectin chimeras all bound to surfaces adsorbed with 2,3-sialyl Lewis x glycolipid or sulfatide (galactosylceramide I3-sulfate) but not to surfaces adsorbed with control sulfated lipids (octadecyl sulfate, sphingosine sulfate). Notably, the L- and P-selectin chimeras but not E-selectin chimera bound to surfaces adsorbed with sulfoglucuronyl glycosphingolipids (SGNL lipids; e.g., IV3glucuronylneolactotetraosylceramide V3-sulfate). These unusual lipids have been reported as antigenic determinants for monoclonal IgM antibodies produced in patients with neuropathy associated with paraproteinemia and react with the mouse monoclonal antibody HNK-1. Binding of L- and P-selectin chimeras to SGNL lipids was specifically inhibited by appropriate anti-selectin antibodies. While binding of all three selectin chimeras to sialyl Lewis x was blocked by removal of calcium, binding to SGNL lipid was only modestly reduced by EDTA. Chemically desulfated SGNL lipid retained binding activity for L- and P-selectin chimeras, while methyl esterification of the glucuronic acid eliminated binding. We conclude that SGNL lipids, unlike sialyl Lewis x and sulfatides, selectively support L- and P-selectin but not E-selectin chimera binding. The presence of SGNL lipids on brain microvascular endothelium (and other endothelia) may implicate these molecules in leukocyte trafficking to the nervous system and elsewhere.