ADAM10-Interacting Tetraspanins Tspan5 and Tspan17 Regulate VE-Cadherin Expression and Promote T Lymphocyte Transmigration.
ADAM10-Interacting Tetraspanins Tspan5 and Tspan17 Regulate VE-Cadherin Expression and Promote T Lymphocyte Transmigration.
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DOI：
10.4049/jimmunol.1600713
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发表时间：
2017-07-15
期刊：
影响因子：
--
通讯作者：
Tomlinson MG
中科院分区：
文献类型：
--
作者：
Reyat JS;Chimen M;Noy PJ;Szyroka J;Rainger GE;Tomlinson MG
血白细胞穿过内皮募集到组织感染部位是炎症的核心，但也促进慢性炎性疾病。解整合素和金属蛋白酶10（ADAM 10）是一种普遍存在的跨膜分子，其通过蛋白水解切割其内皮底物而参与白细胞的迁移。这些包括VE-钙粘蛋白，一种调节内皮屏障功能的同型粘附分子，以及跨膜趋化因子CX 3CL 1和CX CL 16，它们在白细胞上具有受体。然而，内皮细胞ADAM 10在流动下新鲜分离的原代白细胞的迁移中的明确作用尚未得到证实，不同的ADAM 10底物的相对重要性尚不清楚。新出现的证据表明，ADAM 10可以被视为六种不同的分子剪刀，具有不同的底物特异性，这取决于它与六种TspanC 8四跨膜蛋白中的哪一种相关，但TspanC 8在白细胞迁移中仍然没有研究。在目前的研究中，在体外流动试验中，发现原代HUVECs上的ADAM 10敲低损害新鲜分离的人外周血T淋巴细胞的迁移，但不损害中性粒细胞或B淋巴细胞。这种损害是由于延迟的迁移，而不是一个完全的阻滞，并克服了中性粒细胞的存在。纯化的淋巴细胞的再迁移依赖于VE-钙粘蛋白的ADAM 10调节，但不依赖于CX 3CL 1和CXCL 16。Tspan 5和Tspan 17，两个最密切相关的TspanC 8的序列，是唯一的TspanC 8的调节VE-钙粘蛋白的表达和淋巴细胞的迁移所需的。因此，内皮Tspan 5-和Tspan 17-ADAM 10复合物可能通过维持正常VE-钙粘蛋白表达和促进T淋巴细胞迁移来调节炎症。
The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes. However, a definitive role for endothelial ADAM10 in transmigration of freshly isolated primary leukocytes under flow has not been demonstrated, and the relative importance of distinct ADAM10 substrates is unknown. Emerging evidence suggests that ADAM10 can be regarded as six different molecular scissors with different substrate specificities, depending on which of six TspanC8 tetraspanins it is associated with, but TspanC8s remain unstudied in leukocyte transmigration. In the current study, ADAM10 knockdown on primary HUVECs was found to impair transmigration of freshly isolated human peripheral blood T lymphocytes, but not neutrophils or B lymphocytes, in an in vitro flow assay. This impairment was due to delayed transmigration rather than a complete block, and was overcome in the presence of neutrophils. Transmigration of purified lymphocytes was dependent on ADAM10 regulation of VE-cadherin, but not CX3CL1 and CXCL16. Tspan5 and Tspan17, the two most closely related TspanC8s by sequence, were the only TspanC8s that regulated VE-cadherin expression and were required for lymphocyte transmigration. Therefore endothelial Tspan5- and Tspan17-ADAM10 complexes may regulate inflammation by maintaining normal VE-cadherin expression and promoting T lymphocyte transmigration.
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TSPANC8四跨果素差异调节ADAM10底物，Notch活化和ADAM10膜隔室的裂解。
DOI：
10.1007/s00018-015-2111-z
发表时间：
2016-05
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Jouannet S;Saint-Pol J;Fernandez L;Nguyen V;Charrin S;Boucheix C;Brou C;Milhiet PE;Rubinstein E
通讯作者：
Rubinstein E
影响因子：
82.9
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Chimen M;McGettrick HM;Apta B;Kuravi SJ;Yates CM;Kennedy A;Odedra A;Alassiri M;Harrison M;Martin A;Barone F;Nayar S;Hitchcock JR;Cunningham AF;Raza K;Filer A;Copland DA;Dick AD;Robinson J;Kalia N;Walker LSK;Buckley CD;Nash GB;Narendran P;Rainger GE
通讯作者：
Rainger GE
影响因子：
4.4
作者：
Abel, S;Hundhausen, C;Ludwig, A
通讯作者：
Ludwig, A
影响因子：
4.8
作者：
Hermant, B;Bibert, S;Gulino-Debrac, D
通讯作者：
Gulino-Debrac, D
影响因子：
4.8
作者：
Haining, Elizabeth J.;Yang, Jing;Tomlinson, Michael G.
通讯作者：
Tomlinson, Michael G.