The influence of afferent lymphatic vessel interruption on vascular addressin expression.
The influence of afferent lymphatic vessel interruption on vascular addressin expression.
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DOI：
10.1083/jcb.115.1.85
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发表时间：
1991-10
期刊：
影响因子：
--
通讯作者：
Kraal G
中科院分区：
文献类型：
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作者：
Mebius RE;Streeter PR;Brevé J;Duijvestijn AM;Kraal G
组织选择性淋巴细胞归巢在一定程度上是由专门的血管引导的，这些血管定义了淋巴细胞从血液中退出的位置。这些血管，即毛细血管后高内皮小静脉（HEV），存在于有组织的淋巴组织和慢性炎症部位。携带特异性受体（称为归巢受体）的淋巴细胞识别并粘附在高内皮细胞（血管地址）上的假定配体上。粘附后，淋巴细胞通过内皮细胞壁迁移进入有组织淋巴组织。通过传入淋巴供应到达淋巴结的细胞和/或可溶性因子与维持HEV形态和有效的淋巴细胞归巢有关。在本文报道的研究中，我们评估了传入淋巴管中断对淋巴结组成、细胞成分组织的影响；以及血管地址的表达。在传入淋巴管闭塞1周后，HEV壁变平，周围淋巴结地址蛋白的表达从大多数血管的管腔面消失，而在管腔侧保留。此外，由mAb MECA-325定义的hev特异性分化标记物在结论后7 d未检测到。体内归巢研究表明，这些修饰过的血管支持来自血液的最小淋巴细胞流量。阻断后，我们观察到淋巴细胞群发生了巨大变化，在术后7天，淋巴结主要由缺乏周围淋巴结归巢受体LECAM-1的细胞填充。此外，观察到对非淋巴样细胞的影响：单抗MOMA-1定义的荚膜下窦巨噬细胞消失；单克隆抗体NLDC- 145定义的交叉树突状细胞显著减少。这些数据表明，功能正常的传入淋巴在维持正常淋巴结稳态中起主要作用。
Tissue-selective lymphocyte homing is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. These vessels, the post capillary high endothelial venules (HEV), are found in organized lymphoid tissues, and at sites of chronic inflammation. Lymphocytes bearing specific receptors, called homing receptors, recognize and adhere to their putative ligands on high endothelial cells, the vascular addressins. After adhesion, lymphocytes enter organized lymphoid tissues by migrating through the endothelial cell wall. Cells and/or soluble factors arriving in lymph nodes by way of the afferent lymph supply have been implicated in the maintenance of HEV morphology and efficient lymphocyte homing. In the study reported here, we assessed the influence of afferent lymphatic vessel interruption on lymph node composition, organization of cellular elements; and on expression of vascular addressins. At 1 wk after occlusion of afferent lymphatic vessels, HEV became flat walled and expression of the peripheral lymph node addressin disappeared from the luminal aspect of most vessels, while being retained on the abluminal side. In addition, an HEV-specific differentiation marker, defined by mAb MECA-325, was undetectable at 7-d postocclusion. In vivo homing studies revealed that these modified vessels support minimal lymphocyte traffic from the blood. After occlusion, we observed dramatic changes in lymphocyte populations and at 7-d postsurgery, lymph nodes were populated predominantly by cells lacking the peripheral lymph node homing receptor LECAM-1. In addition, effects on nonlymphoid cells were observed: subcapsular sinus macrophages, defined by mAb MOMA-1, disappeared; and interdigitating dendritic cells, defined by mAb NLDC- 145, were dramatically reduced. These data reveal that functioning afferent lymphatics are centrally involved in maintaining normal lymph node homeostasis.