The role of cathepsin X in the migration and invasiveness of T lymphocytes
The role of cathepsin X in the migration and invasiveness of T lymphocytes
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DOI：
10.1242/jcs.023721
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发表时间：
2008-08-15
影响因子：
4
通讯作者：
Kos, Janko
中科院分区：
文献类型：
--
作者：
Jevnikar, Zala;Obermajer, Natasa;Kos, Janko
组织蛋白酶 X 是一种具有羧肽酶活性的溶酶体半胱氨酸蛋白酶。它在免疫系统细胞中高表达，其功能与炎症和免疫反应过程有关。它通过与 β(2) 整联蛋白的相互作用来调节粘附、T 淋巴细胞活化和吞噬作用等过程。为了研究组织蛋白酶 X 在 T 淋巴细胞迁移中的作用，用含有组织蛋白酶 X cDNA 的 pcDNA3 表达载体稳定转染 Jurkat T 淋巴细胞。组织蛋白酶-X 过表达的 T 淋巴细胞表现出极化迁移相关形态，使用细胞间粘附分子 1 (ICAM1) 和基质胶涂层表面增强 2D 和 3D 模型的迁移，并增加同型聚集。组织蛋白酶-X 过表达细胞的侵袭性增加并不涉及细胞外基质的蛋白水解降解。共聚焦显微镜显示，组织蛋白酶 X 的活性成熟形式与淋巴细胞功能相关抗原 1 (LFA-1) 一起共定位于迁移细胞中。这种共定位在尾足的后缘突出处尤其明显，它在 T 淋巴细胞迁移和细胞间相互作用中发挥着重要作用。我们认为组织蛋白酶 X 通过调节 O-2 整合素受体 LFA-1 的活性引起细胞骨架重排并刺激 T 淋巴细胞迁移。
Cathepsin X is a lysosomal cysteine protease exhibiting carboxypeptidase activity. Its expression is high in the cells of immune system and its function has been related to the processes of inflammatory and immune responses. It regulates processes such as adhesion, T lymphocyte activation and phagocytosis through its interaction with beta(2) integrins. To investigate the role of cathepsin X in the migration of T lymphocytes, Jurkat T lymphocytes were stably transfected with a pcDNA3 expression vector containing cathepsin X cDNA. The cathepsin-X-overexpressing T lymphocytes exhibited polarised migration-associated morphology, enhanced migration on 2D and 3D models using intercellular adhesion molecule 1 (ICAM1)- and Matrigel-coated surfaces, and increased homotypic aggregation. The increased invasiveness of cathepsin-X-overexpressing cells does not involve proteolytic degradation of extracellular matrix. Confocal microscopy showed that the active mature form of cathepsin X was colocalised in migrating cells together with lymphocyte-function-associated antigen 1 (LFA-1). The colocalisation was particularly evident at the trailing edge protrusion, the uropod, that has an important role in T lymphocyte migration and cell-cell interactions. We propose that cathepsin X causes cytoskeletal rearrangements and stimulates migration of T lymphocytes by modulating the activity of the O-2 integrin receptor LFA-1.