The alpha(1,3)Fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis
The alpha(1,3)Fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis
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DOI：
10.1016/s0092-8674(00)80137-3
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发表时间：
1996-08-23
期刊：
影响因子：
64.5
通讯作者：
Lowe, JB
中科院分区：
文献类型：
--
作者：
Maly, P;Thall, AD;Lowe, JB
α(1,3)岩藻糖基化寡糖代表 E-和 P-选择素的白细胞反受体以及淋巴结高内皮微静脉 (HEV) 表达的 L-选择素配体的成分。其表达所需的 α(1,3) 岩藻糖基转移酶的身份尚不确定，正如 HEV L-选择素配体活性中对 α(1,3) 岩藻糖基化的要求一样。我们在此证明，α(1,3)岩藻糖基转移酶 Fuc-TVII 缺陷的小鼠表现出白细胞粘附缺陷，其特征是白细胞 E-和 P-选择素配体活性缺失以及 HEV L-选择素配体活性缺陷。选择素配体缺陷的特征是血液白细胞增多、炎症中白细胞外渗受损以及淋巴细胞归巢缺陷。这些观察结果证明了 Fuc-TVII 在 E-、P-和 L-选择素配体生物合成中的重要作用，并暗示该位点可以控制健康和疾病中的白细胞运输。
alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte counterreceptors for E- and P-selectins and of L-selectin ligands expressed by lymph node high endothelial venules (HEV). The identity of the alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain, as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand activity. We demonstrate here that mice deficient in alpha(1,3)fucosyltransferase Fuc-TVII exhibit a leukocyte adhesion deficiency characterized by absent leukocyte E- and P-selectin ligand activity and deficient HEV L-selectin ligand activity. Selectin ligand deficiency is distinguished by blood leukocytosis, impaired leukocyte extravasation in inflammation, and faulty lymphocyte homing. These observations demonstrate an essential role for Fuc-TVII in E-, P-, and L-selectin ligand biosynthesis and imply that this locus can control leukocyte trafficking in health and disease.