The β-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors
The β-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors
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DOI：
10.1016/s0002-9440(10)64035-7
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发表时间：
2001-03-01
影响因子：
6
通讯作者：
Rot, A
中科院分区：
文献类型：
--
作者：
Nibbs, RJB;Kriehuber, E;Rot, A
淋巴管在将液体和白细胞从组织引导到次级淋巴器官中起重要作用。除了驱动白细胞从血液中流出之外，已经表明趋化因子有助于通过趋化剂进行白细胞再循环。以前，我们已经证明了几种促炎β-趋化因子的结合位点在人真皮中的内皮细胞（EC）上发现，使用MIP-1 α同种型MIP-1 α P，我已经扩展了这些研究，以进一步支持这样的论点，即原位趋化因子与传入神经递质的结合表现出类似于在体外观察到的混杂的β-趋化因子受体D 6。我们已经产生了人D 6的单克隆抗体，并显示D 6的免疫反应性的EC内衬传入神经，证实了这样的染色系列皮肤切片与podoplanin，一个已知的淋巴EC标记物的抗体。与此同时，在皮肤上的原位杂交与反义D 6探针表明D 6 mRNA的表达的淋巴管内皮细胞。D 6-免疫反应阳性物质在小肠、大肠和阑尾的粘膜和粘膜下层中也很丰富，但在其他几个受试器官中未观察到。在淋巴结中，D 6免疫反应性存在于传入纤维上，也存在于被膜下和髓窦中。扁桃体淋巴窦也呈D 6阳性。外周血细胞和血管内皮细胞和高内皮微静脉始终不与抗D 6抗体反应。此外，我们已经证明，D 6免疫反应性是检测到在一些恶性血管肿瘤，这表明他们可能是来自，或表型相似，淋巴EC。这是淋巴管内皮细胞表达趋化因子受体的第一个证明，并表明D 6可能影响趋化因子驱动的白细胞再循环通过血管内皮细胞，并修改假定的趋化因子对血管肿瘤的发展和生长的影响。
The lymphatic vessels (lymphatics) play an important role in channeling fluid and leukocytes from the tissues to the secondary lymphoid organs. In addition to driving leukocyte egress from blood, chemokines have been suggested to contribute to leukocyte recirculation via the lymphatics. Previously, we have demonstrated that binding sites for several pro-inflammatory beta -chemokines are found on the endothelial cells (ECs) of lymphatics in human dermis, sere, using the MIP-1 alpha isoform MIP-1 alphaP, me have extended these studies to further support the contention that the in situ chemokine binding to afferent lymphatics exhibits specificity akin to that observed in vitro with the promiscuous beta -chemokine receptor D6. We have generated monoclonal antibodies to human D6 and showed D6 immunoreactivity on the ECs Lining afferent lymphatics, confirmed as such by staining serial skin sections with antibodies against podoplanin, a known lymphatic EC marker. In parallel, in situ hybridization on skin with antisense D6 probes demonstrated the expression of D6 mRNA by lymphatic ECs. D6-immunoreactive lymphatics were also abundant in mucosa and submucosa of small and large intestine and appendix, but not observed in several other organs tested. In lymph nodes, D6 immunoreactivity was present on the afferent lymphatics and also in subcapsular and medullary sinuses. Tonsilar lymphatic sinuses were also D6-positive. Peripheral blood cells and the ECs of blood vessels and high endothelial venules were consistently nonreactive with anti-D6 antibodies. Additionally, we have demonstrated that D6 immunoreactivity is detectable in some malignant vascular tumors suggesting they may be derived from, or phenotypically similar to, lymphatic ECs. This is the first demonstration of chemokine receptor expression by lymphatic ECs, and suggests that D6 may influence the chemokine-driven recirculation of leukocytes through the lymphatics and modify the putative chemokine effects on the development and growth of vascular tumors.