In vivo analysis of molecular mechanism of lymphocyte migration in Peyer's patch

派尔氏淋巴结淋巴细胞迁移分子机制的体内分析

基本信息

批准号：
06454265
负责人：
MIURA Soichiro
金额：
$ 3.65万
依托单位：
Keio University, School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Gut associated lymphoid tissue (GALT) plays an important role for intestinal mucosal defense against dietary and bacterial antigens. In this study, we have established an observatory system of lymphocyte migration in rat Peyer's patches using intravital fluorescence microscopy. Fluorescence labeled lymphocytes adhered to the postcapillary venules (PCV) of Peyer's patches after transient rolling along venular walls. Lymphocytes sticking to the venules increased in number at 10-20 minutes, with preferential adherence of CD4+ cells to venules of 25-50 mum and adherence of B cells to the venules of a wider size range. In this sticking process, adhesion molecules, alpha4-intgerin, L-selectin and CD18/ICAM-1 are shown to be involved. Especially we demonstrated that alpha4-integrin molecule plays a critical role in the early stages of T lymphocyte migration in Peyer's patches. After 30 min, lymphocytes started to extravasate from PCV moved into the interstitium. B cells migrated from venules more quickly than CD4+ cells. Subsequently T lymphocytes preferentially appeared in parafollicular microlymphatics, while few B cells were transported to lymphatics. We also found that alpha4-integrin plays a significant role in the process of transendothelial migration of T lymphocytes in PCV of Peyer's patches. Fat absorption significantly enhanced the rolling and sticking of T cells and subsequent migration into microlymphatics. On the other hand, vasoactive intestinal peptide (VIP) significantly inhibited the transendothelial migration and lymphatic transport without affecting lymphocyte adherence to PCV.By this study, we were able to demonstrate the sequential migration process of lymphocye subpopulations and obtained informations about their regulatory mechanisms.

肠道相关淋巴组织（GALT）在肠粘膜防御饮食和细菌抗原方面发挥着重要作用。在这项研究中，我们利用活体荧光显微镜建立了大鼠派尔氏淋巴集结中淋巴细胞迁移的观察系统。荧光标记的淋巴细胞在沿着小静脉壁短暂滚动后粘附在派尔氏集结的毛细血管后小静脉（PCV）上。粘附在小静脉上的淋巴细胞数量在10-20分钟时增加，CD4+细胞优先粘附在25-50μm的小静脉上，B细胞粘附在更宽尺寸范围的小静脉上。在这个粘附过程中，粘附分子、α4-整合素、L-选择素和CD18/ICAM-1被证明参与其中。特别是我们证明了α4-整合素分子在派尔氏淋巴结T淋巴细胞迁移的早期阶段发挥着关键作用。 30分钟后，淋巴细胞开始从PCV渗出进入间质。 B 细胞从微静脉迁移的速度比 CD4+ 细胞更快。随后T淋巴细胞优先出现在滤泡旁微淋巴管中，而很少有B细胞被转运至淋巴管。我们还发现α4-整合素在派尔氏淋巴结PCV中T淋巴细胞跨内皮迁移过程中发挥重要作用。脂肪吸收显着增强了 T 细胞的滚动和粘附以及随后迁移到微淋巴管的能力。另一方面，血管活性肠肽（VIP）显着抑制跨内皮迁移和淋巴转运，而不影响淋巴细胞对PCV的粘附。通过本研究，我们能够证明淋巴细胞亚群的顺序迁移过程并获得有关其调节机制的信息。