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 anti-cathepsin 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 W-expressing cells was studied in gastrointestinal tissue specimens using the antibody CW-401B1. All cathepsin W-positive cells had a 'lymphocyte phenotype'. Notably, samples from patients suffering from chronic inflammatory bowel disease (Crohn's disease, CD; ulcerative coliltis, UC) or autoimmune gastritis revealed variable amounts of cathepsin W-expressing cells. The relative portion of cathepsin W-positive cells among the infiltrating leukocytes (determined by CD45) differed remarkably. In autoimmune gastritis, cathepsin W-expressing 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 pro-inflammatory cytokines TNF-alpha and IFN-gamma can regulate cathepsin W gene expression in NK-92 cells. Both pro-inflammatory cytokines had only little effect on the cathepsin W gene expression of these cells.