Effects of α1‐acid Glycoprotein Fucosylation on its Ca2+ Mobilizing Capacity in Neutrophils
Effects of α1‐acid Glycoprotein Fucosylation on its Ca2+ Mobilizing Capacity in Neutrophils
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α1-酸性糖蛋白岩藻糖基化对其中性粒细胞Ca2+动员能力的影响
DOI：
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发表时间：
2009
影响因子：
3.7
通讯作者：
P. Påhlsson
中科院分区：
文献类型：
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作者：
L. Levander;P. Gunnarsson;Magnus Grenegård;I. Rydén;P. Påhlsson
我们最近发现，急性时相蛋白 α1 酸性糖蛋白 (AGP) 通过与中性粒细胞受体 siglec-5 和/或 siglec-14 的唾液酸依赖性相互作用，诱导中性粒细胞中胞质钙浓度 [Ca2+]i 升高。虽然 siglec-5 和 siglec-14 对唾液酸化寡糖结构（包括末端 α2-3 或 α2-6 连接唾液酸的两种结构）具有相对广泛的特异性，但与岩藻糖基化表位唾液酸路易斯 x (SLex) 的亲和力明显降低。岩藻糖基化增加导致 AGP 上 SLex 表达增加，通常与炎症状况相关。在本研究中，我们研究了 SLex 表达增加是否会影响 AGP 的 Ca2+ 动员作用。与正常岩藻糖基化的 AGP 相比，从未经治疗的慢性关节炎症患者中分离出的岩藻糖含量升高的 AGP 显示出对中性粒细胞的 [Ca2+]i 调节作用降低。此外，通过体外岩藻糖基化产生的超岩藻糖基化 AGP 形式（因此 SLex 表达升高）不能引起中性粒细胞中 [Ca2+]i 的增加。通过显示携带具有末端 α2-3 或 α2-6 连接唾液酸的寡糖的合成糖复合物能够模拟 AGP 的 Ca2+ 动员作用，而携带 SLex 的合成糖复合物却不能，进一步加强了 AGP 碳水化合物部分在调节中性粒细胞反应中的作用。基于这些数据，我们得出结论，增加岩藻糖基化可以改变 AGP 诱导中性粒细胞信号传导的能力，并进一步支持 AGP 寡糖链在炎症过程中调节白细胞功能中的重要作用。
We recently showed that the acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in cytosolic calcium concentration, [Ca2+]i, in neutrophils through sialic acid dependent interactions with the neutrophil receptors siglec‐5 and/or siglec‐14. Whereas both siglec‐5 and siglec‐14 have a relatively broad specificity for sialylated oligosaccharide structures, including both structures with terminal α2–3 or α2–6 linked sialic acid, there is a markedly reduced affinity to the fucosylated epitope sialyl Lewis x (SLex). Increased fucosylation, leading to increased expression of SLex on AGP is commonly associated with inflammatory conditions. In the present study, we investigated whether an increased SLex expression would affect the Ca2+‐mobilizing effect of AGP. AGP with elevated fucose content isolated from patients with untreated chronic joint inflammation showed a decreased [Ca2+]i modulatory effect on neutrophils compared to normally fucosylated AGP. Furthermore a hyperfucosylated AGP form produced by in vitro fucosylation, that consequently had an elevated expression of SLex, could not elicit a [Ca2+]i increase in neutrophils. The role of the carbohydrate portion of AGP in modulating neutrophil responses was further strengthened by showing that synthetic glycoconjugates carrying oligosaccharides with terminal α2–3 or α2–6 linked sialic acid were able to mimic the Ca2+‐mobilizing effect of AGP whereas a synthetic glycoconjugate carrying SLex was not. Based on these data, we conclude that increased fucosylation can alter the ability of AGP to induce neutrophil signalling and further supports an important role of the oligosaccharide chains of AGP in the modulation of leukocyte functions during an inflammatory process.
人血浆α1-酸性糖蛋白——生化特性、氨基酸序列和碳水化合物部分的结构、变体和多态性。
DOI：
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发表时间：
1989
期刊：
Progress in clinical and biological research
影响因子：
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作者：
Schmid,K
通讯作者：
Schmid,K