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Catabolic pathways for streptokinase, plasmin, and streptokinase activator complex in mice. In vivo reaction of plasminogen activator with alpha 2-macroglobulin.

Publication ,  Journal Article
Gonias, SL; Einarsson, M; Pizzo, SV
Published in: J Clin Invest
August 1982

The catabolic pathways of streptokinase, plasmin, and activator complex prepared with human plasminogen were studied in mice. (125)I-streptokinase clearance occurred in the liver and was 50% complete in 15 min. Incubation with mouse plasma had no effect on the streptokinase clearance rate. Complexes of plasmin and alpha(2)-plasmin inhibitor were eliminated from the plasma by a specific and saturable pathway. Competition experiments demonstrated that this pathway is responsible for the clearance of injected plasmin. Streptokinase-plasminogen activator complex formed with either (125)I-plasminogen or (125)I-streptokinase cleared in the liver at a significantly faster rate than either of the uncomplexed proteins (50% clearance in <3 min). Streptokinase incubated with human plasma also demonstrated this accelerated clearance. p-Nitrophenyl-p'-guanidinobenzoate-HCl or pancreatic trypsin inhibitor-treated complex cleared slowly compared with untreated complex independent of which protein was radiolabeled. Significant competition for clearance was demonstrated between alpha(2)-macroglobulin-trypsin and activator complex only when the plasmin(ogen) was the radiolabeled moiety. Large molar excesses of alpha(2)-plasmin inhibitor-plasmin failed to retard the clearance of activator complex. Hepatic binding of streptokinase-plasmin, in liver perfusion experiments, was dependent upon prior incubation with plasma (8-10% uptake compared to a background of approximately 2.5%). Substitution of human alpha(2)-macroglobulin for plasma also resulted in binding when the incubation was performed for 10 min at 37 degrees C (7.5%). Electrophoresis experiments confirmed the transfer of 0.8 mol plasmin/mol alpha(2)-macroglobulin when activator complex was incubated at 37 degrees C with alpha(2)-macroglobulin for 40 min. Streptokinase transfer from activator complex to alpha(2)-macroglobulin was negligible. The in vivo clearance of activator complex is proposed to involve active attack of the complex on the alpha(2)-macroglobulin "bait region," resulting in facilitated plasmin transfer. Dissociated streptokinase is rapidly bound and cleared by sites in the liver.

Duke Scholars

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

August 1982

Volume

70

Issue

2

Start / End Page

412 / 423

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • alpha-2-Antiplasmin
  • Tissue Distribution
  • Time Factors
  • Streptokinase
  • Plasminogen Activators
  • Perfusion
  • Mice
  • Metabolic Clearance Rate
  • Liver
 

Citation

APA
Chicago
ICMJE
MLA
NLM

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

August 1982

Volume

70

Issue

2

Start / End Page

412 / 423

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • alpha-2-Antiplasmin
  • Tissue Distribution
  • Time Factors
  • Streptokinase
  • Plasminogen Activators
  • Perfusion
  • Mice
  • Metabolic Clearance Rate
  • Liver