Intravital observation of adhesion of lamina propria lymphocytes to microvessels of small intestine in mice
Intravital observation of adhesion of lamina propria lymphocytes to microvessels of small intestine in mice
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DOI：
10.1053/gast.2002.31899
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发表时间：
2002-03-01
期刊：
影响因子：
29.4
通讯作者：
Ishii, H
中科院分区：
文献类型：
--
作者：
Fujimori, H;Miura, S;Ishii, H
背景与目的：虽然淋巴细胞通过肠黏膜的再循环对特异性免疫防御很重要，但固有层淋巴细胞（LPLs）的归巢机制尚不清楚。本研究的目的是在活体显微镜下比较来自肠道固有层的T淋巴细胞和来自脾脏的T淋巴细胞在小鼠肠粘膜中淋巴细胞-内皮细胞识别和结合的动态过程。方法：从小肠和脾脏的非淋巴区分离的LPLs （SPL）进行荧光标记并注射到受体小鼠颈静脉。活体荧光显微镜下观察绒毛黏膜微血管和回肠Peyer’s patches，观察抗黏附-分子抗体对淋巴细胞内皮相互作用的影响。结果：lpl在绒毛尖端的微血管中大量积累，而在Peyer斑块的粘膜下小静脉或毛细血管后小静脉中则没有，在这些地方，lpl有选择性地迁移。抗- 7整合素几乎完全抑制LPLs在绒毛尖端的积累，抗-黏膜定位蛋白细胞粘附分子1 （MAdCAM-1）和抗- α - 4整合素显著抑制LPLs在绒毛尖端的积累。绒毛粘膜微血管中可见MAdCAM-1的显著表达。一些细胞粘附在非淋巴粘膜上，但大多数很快脱落。结论：在体内首次发现，来自固有层而非脾脏的T淋巴细胞选择性粘附在肠绒毛尖端微血管上，主要通过alpha4beta7和MAdCAM-1粘附，而不粘附在Peyer’s patches毛细血管后小静脉上。
Background & Aims: Although the recirculation of lymphocytes through the intestinal mucosa is important for the specific immune defense, the homing of lamina propria lymphocytes (LPLs) has not been clearly understood. The aim of this study is to compare, under an intravital microscope, the dynamic process of lymphocyte-endothelium recognition and binding in the murine intestinal mucosa of T lymphocytes from the lamina propria of intestine to that of T lymphocytes from the spleen. Methods: LPLs isolated from nonlymphoid areas of the small intestine and spleen (SPL) were fluorescence-labeled and injected into a jugular vein of recipient mice. Microvessels of the villus mucosa and ileal Peyer's patches were observed under an intravital fluorescence microscope, and the effects of anti-adhesion-molecule antibodies on lymphocyte-endothelial interaction were investigated. Results: LPLs accumulated abundantly in the microvessels of villus tips but not in the submucosal venules or postcapillary venules of Peyer's patches, where SPLs migrated selectively. The accumulation of LPLs in the villus tips was almost completely inhibited by anti-beta7-integrin and was significantly inhibited by anti-mucosal addressin cell-adhesion molecule 1 (MAdCAM-1) and anti-alpha4-integrin. Significant MAdCAM-1 expression was observed in the microvessels of the villus mucosa. Some SPLs adhered to the nonlymphoid mucosa, but most soon detached. Conclusions: It was shown in vivo for the first time that T lymphocytes from the lamina propria but not from the spleen adhere selectively, mostly via alpha4beta7 and MAdCAM-1, to the microvessels of villus tips of the intestine, but not to the postcapillary venules of Peyer's patches.