title: Human leukocyte elastase and cathepsin G inactivate factor VII by limited proteolysis.
abstract: The effect of supernatant from phorbol myristate acetate (PMA) stimulated human polymorphonuclear granulocytes (PMN) on human factor VII was studied in vitro. The supernatant caused a rapid loss in factor VII coagulant activity by the action of human leukocyte elastase (HLE) and cathepsin G in the supernatant, as demonstrated by the use of specific inhibitors of the two serine proteases, respectively. Preincubation of the supernatant with the elastase inhibitor and the cathepsin G inhibitor preserved 80% and 25% of the clotting activity, respectively. Calcium protected factor VII completely from the supernatant mediated inactivation. Cathepsin G and HLE purified from PMN each destroyed the coagulant activity of factor VII when added to a non-plasma system. There were, however, no effect on factor VII activity when cathepsin G was added to plasma. Polyacrylamide gel electrophoresis in the presence of SDS indicated that HLE and cathepsin G cleaved the zymogen in the same manner, producing (a) peptide(s) of low molecular mass and a single large product of 48 kDa. Preincubation of factor VII with calcium ions inhibited the proteolytic action of HLE and cathepsin G. It is suggested that HLE and cathepsin G from activated granulocytes may be partly responsible for the loss in factor VII activity that is observed during sepsis.
authors.affiliation: Institute of Medical Biology, University of Tromsø, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Anderssen
authors.forename: H
authors.initials: H
authors.lastname: Halvorsen
authors.forename: S P
authors.initials: SP
authors.lastname: Bajaj
authors.forename: B
authors.initials: B
authors.lastname: Osterud
mesh_terms: D000595:Amino Acid Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000097:blood*; D005167:Factor VII / Q000378:metabolism*; D006098:Granulocytes / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000097:blood*; D012697:Serine Endopeptidases
chemical_list: D005167:Factor VII; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase