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Free access | 10.1172/JCI110631

Catabolic Pathways for Streptokinase, Plasmin, and Streptokinase Activator Complex in Mice: IN VIVO REACTION OF PLASMINOGEN ACTIVATOR WITH α2-MACROGLOBULIN

Steven L. Gonias, Monica Einarsson, and Salvatore V. Pizzo

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710

Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710

Kabi Vitrum AB, Research Department, S-112 87 Stockholm, Sweden

Find articles by Gonias, S. in: PubMed | Google Scholar

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710

Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710

Kabi Vitrum AB, Research Department, S-112 87 Stockholm, Sweden

Find articles by Einarsson, M. in: PubMed | Google Scholar

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710

Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710

Kabi Vitrum AB, Research Department, S-112 87 Stockholm, Sweden

Find articles by Pizzo, S. in: PubMed | Google Scholar

Published August 1, 1982 - More info

Published in Volume 70, Issue 2 on August 1, 1982
J Clin Invest. 1982;70(2):412–423. https://doi.org/10.1172/JCI110631.
© 1982 The American Society for Clinical Investigation
Published August 1, 1982 - Version history
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Abstract

The catabolic pathways of streptokinase, plasmin, and activator complex prepared with human plasminogen were studied in mice. 125I-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 α2-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 125I-plasminogen or 125I-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 α2-macroglobulin-trypsin and activator complex only when the plasmin(ogen) was the radiolabeled moiety. Large molar excesses of α2-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 ∼ 2.5%). Substitution of human α2-macroglobulin for plasma also resulted in binding when the incubation was performed for 10 min at 37°C (7.5%). Electrophoresis experiments confirmed the transfer of 0.8 mol plasmin/mol α2-macroglobulin when activator complex was incubated at 37°C with α2-macroglobulin for 40 min. Streptokinase transfer from activator complex to α2-macroglobulin was negligible. The in vivo clearance of activator complex is proposed to involve active attack of the complex on the α2-macroglobulin “bait region,” resulting in facilitated plasmin transfer. Dissociated streptokinase is rapidly bound and cleared by sites in the liver.

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