The glycosylation of human synovial lubricin: implications for its role in inflammation
The glycosylation of human synovial lubricin: implications for its role in inflammation
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DOI：
10.1042/bj20100360
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发表时间：
2010-07-15
影响因子：
4.1
通讯作者：
Karlsson, Niclas G.
中科院分区：
文献类型：
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作者：
Estrella, Ruby P.;Whitelock, John M.;Karlsson, Niclas G.
从两个骨关节炎和两个类风湿性关节炎患者的滑液中分离出酸性蛋白质，并通过MS鉴定。结果发现，在所有样品中最丰富的蛋白质是粘蛋白样蛋白润滑素。通过释放的寡糖的LC（液相色谱）-MS对来自不同患者的润滑素的进一步表征显示核心10-连接的寡糖NeuAc α 2-3Gal β 1-3GalNAc和NeuAc α 2-3Gal β 1-3（NeuAc α 2-6）-GalNAc是润滑素上的主要结构。发现后者在类风湿性关节炎样品中更普遍，表明唾液酸化作为炎症反应的一部分被上调。除了这些主要结构外，还发现了少量的核心2结构，其中最大的是对应于序列NeuAc alpha 2-3Gal beta 1-3（NeuAc alpha 2-3Gal beta 1-3/4GlcNAc beta 1-6）GalNAc的二唾液酸化六糖。还发现小比例的核心2寡糖携带硫酸根。润滑素呈现反映关节组织状态的复杂糖基化的能力使得润滑素成为炎性寡糖表位的候选载体。特别地，显示来自发炎的关节炎组织的润滑素被抗体MECA-79识别，并且因此携带硫酸化表位，所述硫酸化表位被认为是负责将白细胞募集到炎症部位的L-选择素配体的一部分。
Acidic proteins were isolated from synovial fluid from two osteoarthritic and two rheumatoid arthritic patients and identified by MS. It was found that the most abundant protein in all of the samples was the mucin-like protein lubricin. Further characterization of lubricin from the different patients by LC (liquid chromatography)-MS of released oligosaccharides showed that the core 1 O-linked oligosaccharides NeuAc alpha 2-3Gal beta 1-3GalNAc and NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)-GalNAc were the dominating structures on lubricin. The latter was found to be more prevalent in the rheumatoid arthritis samples, indicating that sialylation is up-regulated as pat of the inflammatory response. In addition to these dominating structures, core 2 structures were also found in low amounts, where the largest was the disialylated hexasaccharide corresponding to the sequence NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-3Gal beta 1-3/4GlcNAc beta 1-6)GalNAc. It was also found that a small proportion of the core 2 oligosaccharides carried sulfate. The ability of lubricin to present complex glycosylation reflecting the state of the joint tissue makes lubricin a candidate as a carrier of inflammatory oligosaccharide epitopes. In particular, it was shown that lubricin from inflamed arthritic tissue was recognized by the antibody MECA-79 and thus carried the sulfated epitope proposed to be part of the L-selectin ligand that is responsible for recruitment of leucocytes to inflammatory sites.