Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow.
Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow.
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DOI：
10.1084/jem.20052543
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发表时间：
2006-06-12
期刊：
影响因子：
--
通讯作者：
Miyasaka M
中科院分区：
文献类型：
--
作者：
Umemoto E;Tanaka T;Kanda H;Jin S;Tohya K;Otani K;Matsutani T;Matsumoto M;Ebisuno Y;Jang MH;Fukuda M;Hirata T;Miyasaka M
淋巴细胞运输到淋巴结（LNs）是由淋巴细胞l -选择素和某些唾液黏液蛋白（统称为外周节点寻址蛋白（PNAd））之间的相互作用启动的，这些唾液黏液蛋白携带由LN高内皮小静脉（HEVs）表达的特定碳水化合物。在这里，我们发现了一种新的hev相关的唾液黏液蛋白，nepmucin（在Peyer’s patches [PPs]中不表达的黏液蛋白），它在LN hev中表达，但在PP hev中未检测到蛋白水平。与传统的唾液黏液蛋白不同，海王星黏液蛋白包含一个单一的v型免疫球蛋白（Ig）结构域和一个黏液蛋白样结构域。利用可溶性l -选择素对LN裂解物亲和纯化的材料，我们发现两个高分子量的neppmucin（75和95 kD）被寡糖修饰，这些寡糖结合l -选择素和hev特异性MECA-79单克隆抗体。电镜分析表明，nepmucin在LN hev延长的管腔微绒毛突中积累。在适当的糖基化后，在生理流动条件下，粘蛋白通过其粘蛋白样结构域支持淋巴细胞滚动。此外，与大多数其他唾液黏液蛋白不同，nepmucin通过其Ig结构域结合淋巴细胞，明显独立于淋巴细胞功能相关抗原1和极晚抗原4，并与细胞间粘附分子1结合促进抗剪切淋巴细胞结合。总之，这些结果表明，在LN hev中，nepmucin可能作为一种双重功能的PNAd，通过不同的功能域介导淋巴细胞滚动和结合。
Lymphocyte trafficking to lymph nodes (LNs) is initiated by the interaction between lymphocyte L-selectin and certain sialomucins, collectively termed peripheral node addressin (PNAd), carrying specific carbohydrates expressed by LN high endothelial venules (HEVs). Here, we identified a novel HEV-associated sialomucin, nepmucin (mucin not expressed in Peyer's patches [PPs]), that is expressed in LN HEVs but not detectable in PP HEVs at the protein level. Unlike conventional sialomucins, nepmucin contains a single V-type immunoglobulin (Ig) domain and a mucin-like domain. Using materials affinity-purified from LN lysates with soluble L-selectin, we found that two higher molecular weight species of nepmucin (75 and 95 kD) were decorated with oligosaccharides that bind L-selectin as well as an HEV-specific MECA-79 monoclonal antibody. Electron microscopic analysis showed that nepmucin accumulates in the extended luminal microvillus processes of LN HEVs. Upon appropriate glycosylation, nepmucin supported lymphocyte rolling via its mucin-like domain under physiological flow conditions. Furthermore, unlike most other sialomucins, nepmucin bound lymphocytes via its Ig domain, apparently independently of lymphocyte function–associated antigen 1 and very late antigen 4, and promoted shear-resistant lymphocyte binding in combination with intercellular adhesion molecule 1. Collectively, these results suggest that nepmucin may serve as a dual-functioning PNAd in LN HEVs, mediating both lymphocyte rolling and binding via different functional domains.
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DOI：
10.1006/bbrc.2001.5539
发表时间：
2001-09-14
影响因子：
3.1
作者：
Luo, K;Zhang, WP;Cao, XT
通讯作者：
Cao, XT
影响因子：
4.4
作者：
Chung, DH;Humphrey, MB;Daws, MR
通讯作者：
Daws, MR
影响因子：
32.4
作者：
Hiraoka, N;Petryniak, B;Fukuda, M
通讯作者：
Fukuda, M
影响因子：
32.4
作者：
BARGATZE, RF;JUTILA, MA;BUTCHER, EC
通讯作者：
BUTCHER, EC
DOI：
10.1073/pnas.89.19.9326
发表时间：
1992-10-01
影响因子：
11.1
作者：
BIERHUIZEN, MFA;FUKUDA, M
通讯作者：
FUKUDA, M