TNF-α increases the carbohydrate sulfation of CD44:: induction of 6-sulfo N-acetyl lactosamine on N- and O-linked glycans
TNF-α increases the carbohydrate sulfation of CD44:: induction of 6-sulfo N-acetyl lactosamine on N- and O-linked glycans
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DOI：
10.1093/glycob/cwf080
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发表时间：
2002-10-01
期刊：
影响因子：
4.3
通讯作者：
Johnson, P
中科院分区：
文献类型：
--
作者：
Delcommenne, M;Kannagi, R;Johnson, P
CD44和硫酸化都与白细胞粘附有关。在单核细胞中，炎性细胞因子肿瘤坏死因子α (tnf - α)刺激CD44硫酸化，这与CD44介导的粘附事件的诱导相关。然而，关于CD44的硫酸化或炎症细胞因子对其的诱导作用知之甚少。我们确定tnf - α诱导CD44的碳水化合物硫酸化。CD44在髓细胞上被证实是一个主要的硫酸酸化细胞表面蛋白。在SR91骨髓细胞系中，CD44的大部分磺化归因于糖胺聚糖硫酸软骨素。然而，tnf - α刺激使CD44的硫酸化增加了两到三倍，这主要归因于CD44上N-和o-链聚糖的硫酸化增加。因此，tnf - α诱导了由硫酸软骨素引起的CD44硫酸化百分比的降低和由N-和o -键硫酸化引起的CD44硫酸化百分比的增加。此外，tnf - α诱导6-磺酰n -乙酰乳胺(LacNAc)/Lewis x在这些细胞上的表达，经神经氨酸酶处理后用单克隆抗体检测。这个6-磺基LacNAc/Lewis x表位在CD44上的n -链和（较小程度上）o -链聚糖上被诱导。这表明CD44在髓细胞中被硫代碳水化合物修饰，tnf - α修饰CD44上发生的硫代碳水化合物的类型和数量。此外，研究表明tnf - α可以诱导6-磺酰N-乙酰氨基葡萄糖在骨髓细胞CD44的N-和o -连接聚糖上的表达。
CD44 and sulfation have both been implicated in leukocyte adhesion. In monocytes, the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) stimulates CD44 sulfation, and this correlates with the induction of CD44-mediated adhesion events. However, little is known about the sulfation of CD44 or its induction by inflammatory cytokines. We determined that TNF-alpha induces the carbohydrate sulfation of CD44. CD44 was established as a major sulfated cell surface protein on myeloid cells. In the SR91 myeloid cell line, the majority of CD44 sulfation was attributed to the glycosaminoglycan chondroitin sulfate. However, TNF-alpha stimulation increased CD44 sulfation two- to threefold, largely attributed to the increased sulfation of N- and O-linked glycans on CD44. Therefore, TNF-alpha induced a decrease in the percentage of CD44 sulfation due to chondroitin sulfate and an increase due to N- and O-linked sulfation. Furthermore, TNF-alpha induced the expression of 6-sulfo N-acetyl lactosamine (LacNAc)/Lewis x on these cells, which was detected by a monoclonal antibody after neuraminidase treatment. This 6-sulfo LacNAc/Lewis x epitope was induced on N-linked and (to a lesser extent) on O-linked glycans present on CD44. This demonstrates that CD44 is modified by sulfated carbohydrates in myeloid cells and that TNF-alpha modifies both the type and amount of carbohydrate sulfation occurring on CD44. In addition, it demonstrates that TNF-alpha can induce the expression of 6-sulfo N-acetyl glucosamine on both N- and O-linked glycans of CD44 in myeloid cells.