Lehmann Joachim C U, Jablonski-Westrich Dorothee, Haubold Uta, Gutierrez-Ramos Jose-C, Springer Timothy, Hamann Alf
Experimentelle Rheumatologie, Universitätsklinik Charité, Humboldt-Universität and Deutsches Rheumaforschungszentrum, Schumannstrasse 21/22, 10117 Berlin, Germany.
J Immunol. 2003 Sep 1;171(5):2588-93. doi: 10.4049/jimmunol.171.5.2588.
The integrin LFA-1 interacts with a variety of ligands termed ICAMs. ICAM-1 and ICAM-2 are both expressed on endothelium and serve as counterreceptors during lymphocyte trafficking. In this study, we analyzed their relative contribution to lymphocyte recirculation through lymph nodes and to recruitment into lung and inflamed skin by blocking mAbs against ICAM-1 and ICAM-2 and mice deficient for ICAM-1. The entry of lymphocytes into peripheral and mesenteric lymph nodes was found to be unaffected by the functional deletion of either ICAM-1 or ICAM-2. However, when both pathways were blocked, recirculation through lymph nodes was strongly reduced. Trapping of lymphocytes in the lung after i.v. injection is partly mediated by LFA-1/ICAM interactions; the data presented in this study show an exclusive role of ICAM-1 in LFA-1-dependent lung trapping. Similarly, ICAM-1, but not ICAM-2, was required for the migration of T effector cells into the inflamed skin. These results indicate that ICAM-1 and ICAM-2 have redundant functions in lymphocyte recirculation through lymph nodes, but ICAM-1 is unique in supporting migration into inflamed sites and trapping within the lung.
整合素淋巴细胞功能相关抗原-1（LFA-1）与多种被称为细胞间黏附分子（ICAMs）的配体相互作用。ICAM-1和ICAM-2均在内皮细胞上表达，并在淋巴细胞迁移过程中作为反受体发挥作用。在本研究中，我们通过针对ICAM-1和ICAM-2的阻断性单克隆抗体以及ICAM-1基因缺陷小鼠，分析了它们对淋巴细胞通过淋巴结再循环以及募集至肺和炎症皮肤中的相对作用。发现淋巴细胞进入外周和肠系膜淋巴结不受ICAM-1或ICAM-2功能缺失的影响。然而，当两条途径均被阻断时，通过淋巴结的再循环则显著减少。静脉注射后淋巴细胞在肺中的滞留部分由LFA-1/ICAM相互作用介导；本研究提供的数据表明ICAM-1在依赖LFA-1的肺滞留中起唯一作用。同样，ICAM-1而非ICAM-2是T效应细胞迁移至炎症皮肤所必需的。这些结果表明，ICAM-1和ICAM-2在淋巴细胞通过淋巴结再循环中具有冗余功能，但ICAM-1在支持淋巴细胞迁移至炎症部位以及滞留在肺内方面具有独特作用。
