An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium.
An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium.
复制标题
炎症引起的白细胞跨淋巴管内皮迁移的机制。
DOI：
10.1084/jem.20051759
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发表时间：
2006-11-27
影响因子：
15.3
通讯作者：
Jackson, David G
中科院分区：
文献类型：
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作者：
Johnson, Louise A;Clasper, Steven;Holt, Andrew P;Lalor, Patricia F;Baban, Dilair;Jackson, David G
抗原提呈细胞和淋巴细胞从发炎的皮肤到传入淋巴的出口对于真皮免疫应答的启动和维持是至关重要的。这种出口是如何实现的，以及细胞如何穿过淋巴管的不同内皮尚不清楚。我们发现，炎症细胞因子触发激活真皮淋巴管内皮细胞（LEC），导致表达的关键白细胞粘附受体细胞间粘附分子1（ICAM-1），血管细胞粘附分子1（VCAM-1），E-选择素，以及一个离散的面板的趋化因子和其他潜在的调节白细胞迁移。此外，我们表明，ICAM-1和VCAM-1诱导的皮肤接触超敏反应的小鼠皮肤淋巴管中，它们介导的树突状细胞（DC）通过传入神经系统的淋巴结贩运。最后，我们发现肿瘤坏死因子α刺激DC粘附和真皮LEC单层的迁移，并且该过程被ICAM-1和VCAM-1粘附阻断单克隆抗体有效地抑制。这些结果揭示了CAM介导的机制，招募白细胞的淋巴结炎症和突出的过程中，淋巴细胞的迁移作为一个潜在的新的目标，为癌症治疗。
The exit of antigen-presenting cells and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such an exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels are unknown. We show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LECs), leading to expression of the key leukocyte adhesion receptors intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of dendritic cells (DCs) via afferent lymphatics. Lastly, we show that tumor necrosis factor α stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking monoclonal antibodies. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for antiinflammatory therapy.