DISTINCT ROLES OF L-SELECTIN AND INTEGRINS ALPHA-4-BETA-7 AND LFA-1 IN LYMPHOCYTE HOMING TO PEYERS PATCH-HEV IN-SITU - THE MULTISTEP MODEL CONFIRMED AND REFINED

DISTINCT ROLES OF L-SELECTIN AND INTEGRINS ALPHA-4-BETA-7 AND LFA-1 IN LYMPHOCYTE HOMING TO PEYERS PATCH-HEV IN-SITU - THE MULTISTEP MODEL CONFIRMED AND REFINED
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DOI:
10.1016/1074-7613(95)90162-0
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发表时间:
1995-07-01
期刊:
影响因子:
32.4
通讯作者:
BUTCHER, EC
BUTCHER, EC
中科院分区:
医学1区
文献类型:
--
作者:
BARGATZE, RF;JUTILA, MA;BUTCHER, EC

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循环中的淋巴细胞通过高内皮微静脉(HEV)聚集在粘膜淋巴器官Peyer‘s Patches(PP)中。原位分析显示,输注的淋巴结细胞(LNC)与PP-HEV以一系列重叠的黏附事件相互作用:L-选择素(CD62L)和GT;α4β7启动相互作用,L-选择素和α4β7都参与滚动,Gal连锁激活触发停滞,这需要α4β7和LFA-1。阿尔法4测试版7极大地降低了滚动速度,似乎是LFA-1交战所必需的。与静止的LNC相比,预激活的LNC或α4β7(Hi)淋巴瘤细胞在PP-HEV中只需要α4β7就能停止。α4、β7和L-选择素的主要PP-HEV配基是MAD-CAM-1的粘膜地址。这些结果验证了多分子黏附/决定级联在生理性淋巴细胞-内皮识别中的概念,定义了α4整合素作为选择素和β2整合素依赖事件之间的“桥梁”的新角色,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。
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 Gal-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 7(hi) 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.