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L-选择素、整合素α4β7和淋巴细胞功能相关抗原-1(LFA-1)在淋巴细胞原位归巢至派尔集合淋巴结-高内皮微静脉中的不同作用:多步骤模型得到证实和完善。

Distinct roles of L-selectin and integrins alpha 4 beta 7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: the multistep model confirmed and refined.

作者信息

Bargatze R F, Jutila M A, Butcher E C

机构信息

Department of Pathology, Stanford University School of Medicine, California 94305, USA.

出版信息

Immunity. 1995 Jul;3(1):99-108. doi: 10.1016/1074-7613(95)90162-0.

DOI:10.1016/1074-7613(95)90162-0
PMID:7542550
Abstract

Circulating lymphocytes home to the mucosal lymphoid organs, Peyer's patches (PP), through high endothelial venules (HEV). In situ analyses revealed that transfused lymph node cells (LNCs) interact with PP-HEV in a series of overlapping adhesion events: L-selectin (CD62L) > alpha 4 beta 7 initiates interaction, L-selectin and alpha 4 beta 7 both participate in rolling, and G alpha i-linked activation triggers arrest that requires both alpha 4 beta 7 and LFA-1. alpha 4 beta 7 dramatically reduces rolling velocity, and appears to be required for engagement of LFA-1. In contrast with resting LNC, preactivated LNC or alpha 4 beta 7hi lymphoma cells require only alpha 4 beta 7 for arrest in PP-HEV. The predominant PP-HEV ligand for alpha 4 beta 7 but also apparently for L-selectin is the mucosal addressin MAd-CAM-1. These results validate the concept of multimolecular adhesion/decision cascades in physiologic lymphocyte-endothelial recognition, define a novel role for alpha 4 integrins as a "bridge" between selectin and beta 2 integrin-dependent events, and reemphasize the potential for direct adhesion through preactivated alpha 4 integrins alone.

摘要

循环淋巴细胞通过高内皮微静脉(HEV)归巢至黏膜淋巴器官——派尔集合淋巴结(PP)。原位分析显示,输注的淋巴结细胞(LNC)在一系列重叠的黏附事件中与PP-HEV相互作用:L-选择素(CD62L)>α4β7启动相互作用,L-选择素和α4β7均参与滚动,而Gαi偶联的激活触发停滞,这需要α4β7和淋巴细胞功能相关抗原-1(LFA-1)两者。α4β7显著降低滚动速度,并且似乎是LFA-1结合所必需的。与静息LNC不同,预激活的LNC或α4β7高表达的淋巴瘤细胞在PP-HEV中停滞仅需要α4β7。α4β7以及显然还有L-选择素的主要PP-HEV配体是黏膜定居素细胞黏附分子-1(MAd-CAM-1)。这些结果验证了生理淋巴细胞-内皮识别中多分子黏附/决策级联的概念,定义了α4整合素作为选择素和β2整合素依赖性事件之间“桥梁”的新作用,并再次强调了仅通过预激活的α4整合素直接黏附的可能性。

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