The role of cathepsin X in the migration and invasiveness of T lymphocytes.
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 beta2 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 beta2 integrin receptor LFA-1.
Jevnikar
Zala
Z
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
Obermajer
Natasa
N
Bogyo
Matthew
M
Kos
Janko
J
D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018929:Cell Culture Techniques; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics*; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D019169:Jurkat Cells; D007797:Laminin / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008954:Models, Biological; D011509:Proteoglycans / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation
D004338:Drug Combinations; D007797:Laminin; D016169:Lymphocyte Function-Associated Antigen-1; D011509:Proteoglycans; C059485:matrigel; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K