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首页> 外文期刊>Developmental immunology >In vitro studies on the trafficking of dendritic cells through endothelial cells and extra-cellular matrix.
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In vitro studies on the trafficking of dendritic cells through endothelial cells and extra-cellular matrix.

机译：树突状细胞通过内皮细胞和细胞外基质运输的体外研究。

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Dendritic cells (DC) are antigen presenting cells (APC) with the unique ability to initiate an immune response. Immature DC are localized in peripheral tissues where they exert a sentinel function for incoming antigens (Ag). After Ag capture and exposure to inflammatory stimuli DC undergo maturation and migrate to regional lymph nodes where the presentation of antigenic peptides to T lymphocytes takes place. Thus their correct functioning as APC involves localization in tissues and trafficking via the lymph or blood to lymphoid organs. In the present study we have investigated the ability of DC to interact in vitro with human vascular endothelial cells (EC) and extracellular matrix (ECM). DC are differentiated from monocytes by in vitro exposure to GM-CSF and IL-13 for 7 days. In adhesion assays a considerable proportion of DC binds to resting EC monolayers and this adhesion is inhibited by anti-CD11a and CD11b, but not anti-CD11c mAbs. Binding to a natural ECM, derived from cultured EC involves VLA-4 and VLA-5 integrins. In a transmigration assay, 10% of input cells are able to cross the EC monolayer in the absence of exogenous stimuli. The amount of DC transmigrated through a monolayer of EC was increased of 2-3 fold by C-C chemokines RANTES, MIP1alpha, and MIP-1beta. Most importantly, in view of the trafficking pattern of these cells, a significant proportion of DC can migrate in a reverse transmigration assay, i.e. across the endothelial basement membrane and subsequently, across endothelial cells. Upon exposure to immune or inflammatory signals peripheral DC undergo maturation and migration to lymphoid organs. Functional maturation is associated with loss of responsiveness to chemokines present at sites of inflammation (e.g. MIP1alpha, MIP1beta and RANTES) and acquisition of a receptor repertoire which renders these cells responsive to signals which guide their localization in lymphoid organs (e.g. MIP3beta). A better understanding of the molecular basis of DC trafficking may provide molecular and conceptual tools to direct and modulate DC localization as a strategy to upregulate and orient specific immunity.
机译：树突状细胞（DC）是具有独特能力启动免疫应答的抗原呈递细胞（APC）。未成熟的DC位于周围组织中，在那里它们对传入的抗原（Ag）发挥前哨作用。 Ag捕获并暴露于炎性刺激后，DC会成熟并迁移到区域淋巴结，在那里抗原肽向T淋巴细胞呈递。因此，它们作为APC的正确功能涉及在组织中的定位以及通过淋巴或血液向淋巴器官的运输。在本研究中，我们研究了DC在体外与人血管内皮细胞（EC）和细胞外基质（ECM）相互作用的能力。通过体外暴露于GM-CSF和IL-13 7天，DC从单核细胞中分化出来。在粘附测定中，相当大比例的DC与静止的EC单层结合，并且这种粘附会被抗CD11a和CD11b抑制，但不会被抗CD11c mAb抑制。与源自培养的EC的天然ECM的结合涉及VLA-4和VLA-5整联蛋白。在迁移试验中，在没有外源刺激的情况下，有10％的输入细胞能够穿过EC单层。通过C-C趋化因子RANTES，MIP1alpha和MIP-1beta，通过单层EC迁移的DC量增加了2-3倍。最重要的是，考虑到这些细胞的运输模式，很大一部分的DC可以在反向转运测定中迁移，即穿过内皮基底膜并随后穿过内皮细胞。暴露于免疫或炎症信号后，外周DC会成熟并迁移至淋巴器官。功能成熟与对炎症部位（例如MIP1alpha，MIP1beta和RANTES）上存在的趋化因子的响应能力丧失以及受体库的获得有关，该受体库使这些细胞对指导其在淋巴器官中定位的信号有响应（例如MIP3beta）。更好地了解DC贩运的分子基础可能会提供分子和概念工具，以指导和调节DC定位，作为上调和定向特异性免疫的策略。

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