Functional involvement of cathepsin W in the cytotoxic activity of NK‐92 cells

FEBS Letters

Wex, Thomas¹  Hartig, Roland²  Wilhelmsen, Skadi¹  Wex, Heike³  Malfertheiner, Peter¹ 

[1] Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany;Institute of Immunology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany;Department of Pediatric Hematology and Oncology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany

关键词: Cathepsin W;    NK cell;    Cell-mediated cytotoxicity;    NK-92;   

DOI  :  10.1016/S0014-5793(03)00895-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Human cathepsin W (lymphopain) is a papain-like cysteine protease of unknown function that is specifically expressed in natural killer (NK) cells and to a lesser extent in cytotoxic T cells (CTL). In order to analyze the functional importance of cathepsin W for the cytotoxic process, we investigated NK-92 cells that have an NK cell-like phenotype and express cathepsin W. NK-92 cells possess strong cytotoxic activity against Jurkat and K562 cells. The cytotoxic activity of NK-92 cells against K562 was decreased in the presence of antisense phosphorothioate oligonucleotides against the cathepsin W-cDNA. Western blot analysis showed that the impaired cytotoxic activity of NK-92 cells was accompanied by reduced amounts of cathepsin W in the antisense-treated cells. In addition, co-cultivation experiments between NK-92 and K562 cells revealed a time-dependent decrease of cathepsin W by Western blot and immunofluorescence analysis during the cytotoxic attack, whereas CD56 expression of NK-92 cells was not affected. During cytotoxic attack, cathepsin W was neither targeted to K562 cells or other subcellular compartments, as shown by immunofluorescence analysis. The decrease of cathepsin W protein was associated with stable cathepsin W transcript levels. Control experiments using HT-29 cells, which are resistant against NK-92-mediated cytotoxicity, showed no change of cathepsin W expression, implying that the decrease of cathepsin W in the NK-92/K562 assay is linked to the cytotoxic process. Although the exact function of cathepsin W with respect to its enzymatic activity and its site of action still needs to be elucidated, our data demonstrate for the first time that cathepsin W is important for cellular cytotoxicity mediated by NK cells.

【 授权许可】

Unknown