Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo.
Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo.
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DOI：
10.4049/jimmunol.152.7.3282
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发表时间：
1994-04
影响因子：
4.4
通讯作者：
A. Hamann;D. Andrew;D. Jablonski‐Westrich;B. Holzmann;E. Butcher
中科院分区：
文献类型：
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作者：
A. Hamann;D. Andrew;D. Jablonski‐Westrich;B. Holzmann;E. Butcher
淋巴细胞通过不同器官的再循环被认为是由粘附分子（“归巢受体”）识别内皮上的组织特异性血管地址素调节的。在这里，我们表明，α 4/β 7-整联蛋白在小鼠淋巴细胞迁移到粘膜部位的关键作用。归巢至派尔集合淋巴结而非外周淋巴结受到针对α 4-整联蛋白链的mAb PS/2的Fab片段、识别α 4/β 7-整联蛋白上的组合表位的mAb DATK 32和针对β 7-链的mAb FIB 30的抑制。Ab也显著减少淋巴细胞向肠的归巢。免疫母细胞向肠道和肠道相关淋巴组织的迁移也涉及α 4/β 7-整联蛋白异源二聚体。另一种抗α 4抗体R1-2在Stamper-Woodruff冷冻切片试验中阻断淋巴细胞与派尔集合淋巴结的结合以及淋巴细胞与VCAM-1和纤连蛋白的粘附，对体内淋巴细胞运输仅有轻微影响。与针对粘膜地址素MAdCAM-1的Ab相反，抗VCAM-1 Ab以及纤连蛋白肽CS-1对向派尔集合淋巴结或肠的迁移没有影响。因此，归巢到肠道相关位点是由α 4/β 7-整联蛋白异二聚体与血管地址素MAdCAM-1相互作用调节的，而不是与纤连蛋白或VCAM-1作为相对结构。所研究的抗整联蛋白抗体对派尔集合淋巴结和肠归巢的抑制仅是部分的。L-选择素还参与小淋巴细胞归巢到粘膜部位，特别是派伊尔集合淋巴结，但基本上不参与胚细胞定位到肠壁中。结果支持α 4/β 7-整联蛋白在淋巴细胞运输至粘膜部位中的主要但非唯一作用。
Lymphocyte recirculation through different organs is thought to be regulated by adhesion molecules ("homing receptors") recognizing tissue-specific vascular addressins on endothelium. Here we show that the alpha 4/beta 7-integrin has a key role in the migration of mouse lymphocytes to mucosal sites. Homing to Peyer's patches but not to peripheral lymph nodes is inhibited by Fab fragments of mAb PS/2 against the alpha 4-integrin chain, by mAb DATK32 recognizing a combinatorial epitope on the alpha 4/beta 7-integrin, and by mAb FIB30 against the beta 7-chain. The Abs significantly reduce homing of lymphocytes to the intestine, as well. The migration of immunoblasts to gut and gut-associated lymphoid tissue also involves the alpha 4/beta 7-integrin heterodimer. Another anti-alpha 4 Ab, R1-2, which blocks lymphocyte binding to Peyer's patches in the Stamper-Woodruff frozen section assay and lymphocyte adhesion to VCAM-1 and fibronectin, has only minor effects on lymphocyte traffic in vivo. Anti-VCAM-1 Ab as well as the fibronectin peptide CS-1 are without influence on the migration to Peyer's patches or intestine, in contrast to Ab against the mucosal addressin MAdCAM-1. Thus, homing to gut-associated sites is regulated by the alpha 4/beta 7-integrin heterodimer interacting with the vascular addressin, MAdCAM-1, and not with fibronectin or VCAM-1 as counterstructures. Inhibition of homing to Peyer's patches and intestine by the anti-integrin Abs studied was only partial. L-selectin also participates in the homing of small lymphocytes to mucosal sites, especially Peyer's patches, but does not contribute substantially to the localization of blasts into the intestinal wall. The results support a major, but not exclusive role of the alpha 4/beta 7-integrin in lymphocyte traffic to mucosal sites.