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Thromb Haemost 1993; 70(03): 414-417
DOI: 10.1055/s-0038-1649596
Original Article
Coagulation
Schattauer GmbH Stuttgart

Human Leukocyte Elastase and Cathepsin G Inactivate Factor VII by Limited Proteolysis

Trude Anderssen
1   The Institute of Medical Biology, University of Tromsø, Tromsø, Norway
,
Hanne Halvorsen
1   The Institute of Medical Biology, University of Tromsø, Tromsø, Norway
,
S Paul Bajaj
2   The Department of Internal Medicine, Saint Louis University Medical Center, St. Louis, MO, USA
,
Bjarne Østerud
1   The Institute of Medical Biology, University of Tromsø, Tromsø, Norway
› Author Affiliations
Further Information

Publication History

Received 08 April 1992

Accepted after revision 14 April 1993

Publication Date:
24 July 2018 (online)

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Summary

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.

 

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