Characterization of novel anti-cathepsin W antibodies and cellular distribution of cathepsin W in the gastrointestinal tract

Human cathepsin W (lymphopain) is a cysteine protease that is restrictively expressed in cytotoxic cells, in particular NK cells. Several anticathepsin W monoclonal antibodies were tested with respect to their capability to detect cathepsin W by Western blot analysis and immunohistochemistry. Subsequently, the distribution of cathepsin Wexpressing cells was studied in gastrointestinal tissue specimens using the antibody CW-401B1. All cathepsin Wpositive cells had a lymphocyte phenotype. Notably, samples from patients suffering from chronic inflammatory bowel disease (Crohns disease, CD; ulcerative coliltis, UC) or autoimmune gastritis revealed variable amounts of cathepsin Wexpressing cells. The relative portion of cathepsin Wpositive cells among the infiltrating leukocytes (determined by CD45) differed remarkably. In autoimmune gastritis, cathepsin Wexpressing cells made up for 65% of all CD45+ cells, whereas the corresponding values for CD and UC were 11% and 6%, respectively. These differences imply a distinct involvement of cytotoxic cells expressing cathepsin W in the pathogenesis among these diseases. Furthermore, it was tested whether the proinflammatory cytokines TNF-alpha and IFN-gamma can regulate cathepsin W gene expression in NK-92 cells. Both proinflammatory cytokines had only little effect on the cathepsin W gene expression of these cells.