An elastase-dependent pathway of plasminogen activation

Raymund Machovich, Whyte G. Owen

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

In reaction mixtures containing Glu-plasminogen, α2-antiplasmin, and tissue plasminogen activator or urokinase, either pancreatic or leukocyte elastase enhances the rate of plasminogen activation by 2 or more orders of magnitude. This effect is the consequence of several reactions, (a) In concentrations on the order of 100 nM, elastase degrades plasminogen within 10 min to yield des-kringle1-4-plasminogen (mini-plasminogen), which is 10-fold more efficient than Glu-plasminogen as a substrate for plasminogen activators. Des-kringle1-4-plasminogen is insensitive to cofactor activities of fibrin(ogen) fragments or an endothelial cell cofactor. (b) Des-kringle1-4-plasmin is one-tenth as sensitive as plasmin to inhibition by α2-antiplasmin: k″ = 106 M-1 s-1 versus 107 M-1 s-1. (c) α2-Antiplasmin is disabled efficiently by elastase, with a k″ of 20000 M-1 s-1. The elastase-dependent reactions are not influenced by 6-aminohexanoate. In diluted (10-fold) blood plasma, the capacity of endogenous inhibitors to block plasmin expression is suppressed by 30 μM elastase. It is proposed that elastases provide an alternative pathway for Glu-plasminogen activation and a mechanism for controlling initiation of fibrinolysis by urokinase-type plasminogen activators.

Original languageEnglish
Pages (from-to)4517-4522
Number of pages6
JournalBiochemistry
Volume28
Issue number10
Publication statusPublished - 1989

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Pancreatic Elastase
Plasminogen
Chemical activation
Antifibrinolytic Agents
Fibrinolysin
Urokinase-Type Plasminogen Activator
Aminocaproates
Leukocyte Elastase
Plasminogen Activators
Endothelial cells
Fibrinolysis
Tissue Plasminogen Activator
Fibrin
Blood
Endothelial Cells
Plasmas
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

An elastase-dependent pathway of plasminogen activation. / Machovich, Raymund; Owen, Whyte G.

In: Biochemistry, Vol. 28, No. 10, 1989, p. 4517-4522.

Research output: Contribution to journalArticle

Machovich, R & Owen, WG 1989, 'An elastase-dependent pathway of plasminogen activation', Biochemistry, vol. 28, no. 10, pp. 4517-4522.
Machovich, Raymund ; Owen, Whyte G. / An elastase-dependent pathway of plasminogen activation. In: Biochemistry. 1989 ; Vol. 28, No. 10. pp. 4517-4522.
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