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.
Buhling
Frank
F
Institute of Immunology, Otto-von-Guericke University Magdeburg, Germany.
Kellner
Udo
U
Guenther
Dagmar
D
Kahl
Stefan
S
Brömme
Dieter
D
Weber
Ekkehard
E
Malfertheiner
Peter
P
Wex
Thomas
T
D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D056664:Cathepsin W; D002403:Cathepsins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004064:Digestive System / Q000201:enzymology*; D005767:Gastrointestinal Diseases / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000201:enzymology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D016207:Cytokines; D002403:Cathepsins; C534187:CTSW protein, human; D056664:Cathepsin W; D003546:Cysteine Endopeptidases