Description:
<jats:p>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.</jats:p>