Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels.
Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels.
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在 DC 穿过发炎淋巴管的过程中，淋巴内皮形成整合素接合的 3D 结构。
DOI：
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发表时间：
2013
影响因子：
6.5
通讯作者：
A. Rouzaut
中科院分区：
文献类型：
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作者：
Á. Teijeira;S. Garasa;R. Pélaez;Arantza Azpilikueta;C. Ochoa;Diego Marré;Magda Rodrigues;C. Alfaro;C. Aubá;S. Valitutti;I. Melero;A. Rouzaut
树突状细胞（DC）穿过淋巴管内皮的迁移对于免疫应答的启动和维持至关重要。在非炎症条件下，DC通过淋巴管内皮细胞（LEC）已被证明是整合素独立的。相比之下，越来越多的证据表明整合素及其配体参与炎症条件下DC穿过淋巴内皮的转运。在这个意义上，我们描述了形成ICAM-1（CD 54）富集的三维结构的LEC/DC接触，因为这些DC坚持发炎的皮肤淋巴管和transmigrate到他们。体外成像显示，炎症条件下ICAM-1聚集在60%粘附DC周围的微绒毛突起上。相反，这些结构在非炎症条件下几乎不形成。此外，ICAM-1富集的微绒毛在促进DC跨内皮迁移和DC在LEC表面爬行中是重要的。微绒毛的形成依赖于DC侧的β-整合素的存在以及整合素对配体的构象亲和力。最后，我们观察到LEC微绒毛结构出现在CCL 21库附近，并且它们的组装被CCL 21中和抗体部分抑制。因此，在炎症条件下，整合素配体在DC周围形成三维膜突起。这些结构为DC从组织向淋巴管腔转运提供了对接位点。
Dendritic cell (DC) transmigration across the lymphatic endothelium is critical for the initiation and sustenance of immune responses. Under noninflammatory conditions, DC transit across the lymphatic endothelial cell (LEC) has been shown to be integrin independent. In contrast, there is increasing evidence for the participation of integrins and their ligands in DC transit across lymphatic endothelium under inflammation. In this sense, we describe the formation of ICAM-1 (CD54)-enriched three-dimensional structures on LEC/DC contacts, as these DCs adhere to inflamed skin lymphatic vessels and transmigrate into them. In vitro imaging revealed that under inflammation ICAM-1 accumulated on microvilli projections surrounding 60% of adhered DCs. In contrast, these structures were scarcely formed in noninflammatory conditions. Furthermore, ICAM-1-enriched microvilli were important in promoting DC transendothelial migration and DC crawling over the LEC surface. Microvilli formation was dependent on the presence of β-integrins on the DC side and on integrin conformational affinity to ligand. Finally, we observed that LEC microvilli structures appeared in close vicinity of CCL21 depots and that their assembly was partially inhibited by CCL21-neutralizing antibodies. Therefore, under inflammatory conditions, integrin ligands form three-dimensional membrane projections around DCs. These structures offer docking sites for DC transit from the tissue toward the lymphatic vessel lumen.
影响因子：
32.4
作者：
Constantin, G;Majeed, M;Laudanna, C
通讯作者：
Laudanna, C
影响因子：
6
作者：
Yao, Li-Chin;Baluk, Peter;McDonald, Donald M.
通讯作者：
McDonald, Donald M.
影响因子：
32.4
作者：
Alvarez, David;Vollmann, Elisabeth H.;von Andrian, Ulrich H.
通讯作者：
von Andrian, Ulrich H.