Book of abstract 2008

Cathepsin X controls migration and invasiveness of T lymphocytes
Zala Jevnikar1, Nataša Obermajer1, Matthew Bogyo2, Janko Kos1 ,3
1Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia; 2Dept. of Pathology,
Stanford University, Stanford, CA 94305-5324, USA; 3Dept. of Biotechnology, Jožef Stefan Institute,
Jamova 39, SI-1000 Ljubljana, Slovenia
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 interaction with β 2
integrins. To investigate the role of cathepsin X in the migration of T lymphocytes, Jurkat
T lymphocytes were stably transfected with the pcDNA3 expression vector containing
cathepsin X cDNA. The cathepsin X up-regulated T lymphocytes exhibited polarized
migration-associated morphology, enhanced migration on 2-D and 3-D models using
intercellular adhesion molecule – 1 (ICAM-1) and Matrigel coated surfaces and increased
homotypic aggregation. The increased invasiveness of cathepsin X up-regulated cells does
not involve proteolytic degradation of extracellular matrix. Confocal microscopy showed
that the active mature form of cathepsin X was co-localized in migrating cells together with
lymphocyte function-associated antigen 1 (LFA-1). The co-localization was particularly
evident at the trailing edge protrusion, the uropod, which plays an important role in T
lymphocyte migration and cell-cell interactions. We propose that cathepsin X causes
cytoskeletal rearrangements and stimulates T lymphocyte migration by modulating the
activity of β 2
integrin receptor LFA-1.
30
l15