Direct induction of complement activation by pharmacologic activation of plasminogen

Coron Artery Dis. 1997 Jan;8(1):9-18. doi: 10.1097/00019501-199701000-00002.


Background: Complement activation occurs in patients with myocardial infarction treated with fibrinolytic agents and plays a critical role in reperfusion injury. This study was designed to determine whether pharmacologic activation of plasminogen directly induces complement activations.

Methods: Whole blood was incubated with plasminogen activators and the plasma was assayed for C3a levels as an indicator of complement activation.

Results: Therapeutic concentrations of tissue-type plasminogen activator, streptokinase, or urokinase increased C3a concentrations from a baseline of approximately 500 ng/ml to an average of 1300-1500 ng/ml with tissue-type plasminogen activator or urokinase, and to an average of approximately 4000 ng/ml with streptokinase (P < 0.01, versus baseline for all plasminogen activators). Plasminogen activation also enhanced complement activation induced by conventional complement activators.

Conclusions: These results indicate that pharmacologic plasminogen activation may exacerbate reperfusion injury either by directly inducing complement activation or by enhancing the activation initiated by other mechanisms, or both.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Specimen Collection
  • Complement Activation / drug effects*
  • Complement C3a / analysis*
  • Fibrinolysin / pharmacology
  • Humans
  • In Vitro Techniques
  • Myocardial Reperfusion Injury / etiology
  • Plasminogen Activators / adverse effects
  • Plasminogen Activators / pharmacology*
  • Time Factors


  • Complement C3a
  • Plasminogen Activators
  • Fibrinolysin