Endothelial alpha 2,6-linked sialic acid inhibits VCAM-1-dependent adhesion under flow conditions.
Endothelial alpha 2,6-linked sialic acid inhibits VCAM-1-dependent adhesion under flow conditions.
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DOI：
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发表时间：
1999-09
影响因子：
4.4
通讯作者：
Yasunori Abe;C. Smith;J. Katkin;L. M. Thurmon;Xudong Xu;Leonardo H. Mendoza;C. Ballantyne
中科院分区：
文献类型：
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作者：
Yasunori Abe;C. Smith;J. Katkin;L. M. Thurmon;Xudong Xu;Leonardo H. Mendoza;C. Ballantyne
我们之前已经证明，在流动条件下，用 IL-1 + IL-4 共刺激内皮细胞可显着抑制 VCAM-1 依赖性粘附。我们假设共刺激细胞表面上的唾液酸可能有助于抑制。 Northern印迹分析表明，在单独的IL-1或IL-4培养的HUVEC中，Gal beta 1-4GlcNAc α 2,6-唾液酸转移酶（ST6N）mRNA上调，但共刺激表达增强，而Gal beta 1-4GlcNAc/Gal beta 1-3GalNAc α2,3-唾液酸转移酶（ST3ON）mRNA水平没有变化。通过唾液酸酶从IL-1 + IL-4共刺激的HUVEC中去除α2,6-和α2,3-连接的唾液酸显着增加了VCAM-1依赖性粘附，而单独去除α2,3-连接的唾液酸没有效果；腺病毒介导的 ST6N 过度表达与共刺激几乎消除了粘附，而这种粘附可通过唾液酸酶逆转。 IL-1 刺激的 HUVEC 的相同治疗没有效果。凝集素印迹显示 VCAM-1 用 α 2,6- 但不是 α 2,3- 连接的唾液酸修饰。然而，α2,6-唾液酸转移酶的过度表达并没有增加VCAM-1上的α2,6连接的唾液酸，但确实增加了其他有待鉴定的蛋白质上的α2,6连接的唾液酸。这些结果表明，通过与 IL-1 + IL-4（而非单独的 IL-1）共刺激可诱导的分子上的 α2,6-连接唾液酸在流动条件下下调 VCAM-1 依赖性粘附。
We have previously shown that costimulation of endothelial cells with IL-1 + IL-4 markedly inhibits VCAM-1-dependent adhesion under flow conditions. We hypothesized that sialic acids on the costimulated cell surfaces may contribute to the inhibition. Northern blot analyses showed that Gal beta 1-4GlcNAc alpha 2, 6-sialyltransferase (ST6N) mRNA was up-regulated in cultured HUVEC by IL-1 or IL-4 alone, but that the expression was enhanced by costimulation, whereas the level of Gal beta 1-4GlcNAc/Gal beta 1-3GalNAc alpha2,3-sialyltransferase (ST3ON) mRNA was unchanged. Removing both alpha 2,6- and alpha 2,3-linked sialic acids from IL-1 + IL-4-costimulated HUVEC by sialidase significantly increased VCAM-1-dependent adhesion, whereas removing alpha 2,3-linked sialic acid alone had no effect; adenovirus-mediated overexpression of ST6N with costimulation almost abolished the adhesion, which was reversible by sialidase. The same treatments of IL-1-stimulated HUVEC had no effect. Lectin blotting showed that VCAM-1 is decorated with alpha 2,6- but not alpha 2,3-linked sialic acids. However, overexpression of alpha 2,6-sialyltransferase did not increase alpha 2,6-linked sialic acid on VCAM-1 but did increase alpha 2,6-linked sialic acids on other proteins that remain to be identified. These results suggest that alpha 2,6-linked sialic acids on a molecule(s) inducible by costimulation with IL-1 + IL-4 but not IL-1 alone down-regulates VCAM-1-dependent adhesion under flow conditions.