Green P J, Yuen C T, Childs R A, Chai W, Miyasaka M, Lemoine R, Lubineau A, Smith B, Ueno H, Nicolaou K C
Glycobiology Group, Northwick Park Hospital, Harrow, Middlesex, UK.
Glycobiology. 1995 Feb;5(1):29-38. doi: 10.1093/glycob/5.1.29.
This communication is concerned with the binding specificity of the leukocyte-adhesion molecule L-selectin (leukocyte homing receptor) towards structurally defined sulphated oligosaccharides of the blood group Le(a) and Le(x) series, and of the glycosaminoglycan series heparin, chondroitin sulphate and keratan sulphate. The recombinant soluble form of the rat L-selectin (L-selectin-IgG Fc chimera) investigated here was shown previously to bind to lipid-linked oligosaccharides 3-O, 4-O and 6-O sulphated at galactose, such as sulphatides and a mixture of 3-sulphated Le(a)/Le(x) type tetrasaccharides isolated from ovarian cystadenoma, as well as to the HNK-1 glycolipid with 3-O sulphated glucuronic acid. In the present study, the L-selectin investigated in both chromatogram binding and plastic microwell binding experiments using neoglycolipids was found to bind to the individual 3-sulphated Le(a) and Le(x) sequences (penta-, tetra- and trisaccharides), and with somewhat lower intensities to their non-fucosylated analogues. Glycosaminoglycan disaccharides of keratan sulphate, heparin and chondroitin sulphate types were also bound by L-selectin in one or both assay systems, leading to the conclusion that clustered glycosaminoglycan oligosaccharides with 6-O sulphation of N-acetylgalactosamine, N-acetylglucosamine or glucosamine, 4-O sulphation of N-acetylgalactosamine, 2-O sulphation of uronic acid, N-sulphation of glucosamine and, to a lesser extent, the non-sulphated uronic acid-containing disaccharides, can support L-selectin adhesion. As inflammatory chemokines (short-range stimulators of lymphocyte migration which trigger integrin activation) are known to bind to endothelial glycosaminoglycans, we propose that the binding of the lymphocyte membrane L-selectin to endothelial glycosaminoglycans may provide a link between the selectin-mediated and integrin-mediated adhesion systems in leukocyte extravasation cascades. The possibility is also raised that lymphocyte L-selectin interactions with glycosaminoglycans may contribute to pathologies of glycosaminoglycan-rich tissues, e.g. cartilage loss in rheumatoid arthritis and inflammatory lesions of the cornea.
本通讯涉及白细胞粘附分子L-选择素（白细胞归巢受体）对血型Le(a)和Le(x)系列以及糖胺聚糖系列肝素、硫酸软骨素和硫酸角质素中结构明确的硫酸化寡糖的结合特异性。本文研究的大鼠L-选择素的重组可溶性形式（L-选择素-IgG Fc嵌合体）先前已被证明可与在半乳糖上3-O、4-O和6-O硫酸化的脂联寡糖结合，如硫苷脂以及从卵巢囊腺瘤中分离出的3-硫酸化Le(a)/Le(x)型四糖混合物，还可与含3-O硫酸化葡萄糖醛酸的HNK-1糖脂结合。在本研究中，在使用新糖脂的色谱结合和塑料微孔板结合实验中研究的L-选择素被发现可与单个3-硫酸化的Le(a)和Le(x)序列（五糖、四糖和三糖）结合，并且与它们的非岩藻糖基化类似物的结合强度略低。硫酸角质素、肝素和硫酸软骨素类型的糖胺聚糖二糖在一种或两种检测系统中也被L-选择素结合，从而得出结论，具有N-乙酰半乳糖胺、N-乙酰葡糖胺或葡糖胺6-O硫酸化、N-乙酰半乳糖胺4-O硫酸化、糖醛酸2-O硫酸化、葡糖胺N-硫酸化以及在较小程度上含非硫酸化糖醛酸的二糖的聚集糖胺聚糖寡糖可以支持L-选择素粘附。由于炎症趋化因子（触发整合素激活的淋巴细胞迁移的短程刺激物）已知可与内皮糖胺聚糖结合，我们提出淋巴细胞膜L-选择素与内皮糖胺聚糖的结合可能在白细胞外渗级联反应中提供选择素介导和整合素介导的粘附系统之间的联系。还提出了淋巴细胞L-选择素与糖胺聚糖相互作用可能导致富含糖胺聚糖的组织发生病变的可能性，例如类风湿性关节炎中的软骨损失和角膜的炎性病变。
