title: Enzymatically active cathepsin B dissociating from its inhibitor complexes is elevated in blood plasma of patients with septic shock and some malignant tumors.
abstract: Using fluorogenic substrates and the specific inhibitor E-64, cysteine proteinase (CP) activity was measured in blood plasma of healthy controls (mean = 35.0 mU/l) and patients with cancer and severe septic shock. Whereas moderately elevated activity was observed in some kinds of cancer (mean = 63.9 mU/l), 10-fold increased CP activity was found in septic shock. The plasma CP activity of sepsis patients paralleled the immunologically determined concentration of elastase-alpha 1-proteinase inhibitor complex. On the basis of its substrate specificity and its Michaelis constant for Z-Phe-Arg-NMec the plasma CP was identified as cathepsin B or a cathepsin B-like proteinase (CBP). Kinetic studies revealed that dilution and competition with substrate effects reversible dissociation of CBP from complexes with plasma inhibitors that are most probably the kininogens. The dissociation of CBP was confirmed by gel chromatographic fractionation of the plasma proteins. The results suggest that active CBP can easily dissociate from its plasma inhibitor complexes in vivo and may be involved in pathogenetic extracellular proteolysis.
authors.affiliation: Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie der Universität München.
authors.forename: I
authors.initials: I
authors.lastname: Assfalg-Machleidt
authors.forename: M
authors.initials: M
authors.lastname: Jochum
authors.forename: W
authors.initials: W
authors.lastname: Klaubert
authors.forename: D
authors.initials: D
authors.lastname: Inthorn
authors.forename: W
authors.initials: W
authors.lastname: Machleidt
mesh_terms: D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000097:blood*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D010455:Peptides / Q000032:analysis; D012772:Shock, Septic / Q000201:enzymology*; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity
chemical_list: D010455:Peptides; D003546:Cysteine Endopeptidases; D002401:Cathepsin B