Laminin isoforms of lymph nodes and predominant role of α5-laminin(s) in adhesion and migration of blood lymphocytes
Laminin isoforms of lymph nodes and predominant role of α5-laminin(s) in adhesion and migration of blood lymphocytes
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DOI：
10.1189/jlb.0108048
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发表时间：
2008-09-01
影响因子：
5.5
通讯作者：
Patarroyo, Manuel
中科院分区：
文献类型：
--
作者：
Gorfu, Gezahegn;Virtanen, Ismo;Patarroyo, Manuel
在外渗和淋巴结（LN）内，血液淋巴细胞与层粘连蛋白（Lms）相互作用，层粘连蛋白是血管基底膜（BM）和网状纤维（RF）的主要成分，是一种纤维状细胞外基质。然而，这些层粘连蛋白同种型的身份和作用知之甚少。通过使用共聚焦显微镜检查人类LN，我们发现，BM的高内皮小静脉（HEV）表达层粘连蛋白α 3，α 4，α 5，β 1，β 2，和γ 1链，并发现相同的链，除了α 2，在RF。在覆盖所有Lm α链的层粘连蛋白同种型的功能研究中，α 5-层粘连蛋白（Lm-511）是人血淋巴细胞中最能促进粘附和迁移的同种型，其次是α 3-（Lm-332）和α 4-（Lm-411）层粘连蛋白，淋巴细胞使用α 6 β 1整联蛋白作为α 5-层粘连蛋白的主要受体。此外，Lm-511强烈地共刺激T细胞增殖，并且血液淋巴细胞能够在刺激后分泌α 4-和α 5-层粘连蛋白。层粘连蛋白α 4缺陷小鼠的LN细胞数量与野生型相比没有显著差异。本研究证明了α 5-层粘连蛋白在血液淋巴细胞生物学中的主要作用，并鉴定了LN层粘连蛋白及其在血液淋巴细胞中的整合素受体。
During extravasation and within lymph nodes (LNs), blood lymphocytes interact with laminins (Lms), major components of vascular basement membranes (BMs) and of reticular fibers (RFs), a fibrillar extracellular matrix. However, the identity and role of these laminin isoform(s) are poorly known. By using confocal microscopy examination of human LNs, we show that BMs of high endothelial venules (HEVs) express laminin alpha 3, alpha 4, alpha 5, beta 1, beta 2, and gamma 1 chains and that the same chains, in addition to alpha 2, are found in RFs. In functional studies with laminin isoforms covering all Lm alpha chains, alpha 5-laminin (Lm-511) was the most adhesion-and migration-promoting isoform for human blood lymphocytes, followed by alpha 3-(Lm-332) and alpha 4-(Lm-411) laminins, and the lymphocytes used the alpha 6 beta 1 integrin as the primary receptor for the alpha 5-laminin. Moreover, Lm-511 strongly co-stimulated T cell proliferation, and blood lymphocytes were able to secrete alpha 4- and alpha 5-laminins following stimulation. The LN cell number in laminin alpha 4-deficient mice compared with wild-type did not differ significantly. This study demonstrates a predominant role for alpha 5-laminin(s) in blood lymphocyte biology and identifies LN laminins and their integrin receptors in blood lymphocytes.