A Hamster Antibody to the Mouse Fibrinogen Chain Inhibits Platelet-fibrinogen Interactions and FXIIIa-mediated Fibrin Cross-linking, and Facilitates Thrombolysis

Markéta JirouȈsková; Susan S. Smyth; Bohdan Kudryk; Barry S. Coller

doi:10.1055/s-0037-1616532

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(04): 1047-1056
DOI: 10.1055/s-0037-1616532

Special Article

Schattauer GmbH

A Hamster Antibody to the Mouse Fibrinogen Chain Inhibits Platelet-fibrinogen Interactions and FXIII_a-mediated Fibrin Cross-linking, and Facilitates Thrombolysis

Markéta JirouȈsková

¹Department of Medicine, Mount Sinai School of Medicine, New York, NY

,

Susan S. Smyth

¹Department of Medicine, Mount Sinai School of Medicine, New York, NY

,

Bohdan Kudryk

²Laboratory of Blood Coagulation Biochemistry, New York Blood Center, New York, NY, USA

,

Barry S. Coller^*

¹Department of Medicine, Mount Sinai School of Medicine, New York, NY

› Author Affiliations

Abstract

Summary

Murine models employing genetically altered mice have the potential to provide important new information about the hemostatic system, but before such data can be extrapolated to humans it is necessary to define the similarities and differences between murine and human hemostasis. After establishing the similarities of murine fibrinogen to human fibrinogen in its pattern of proteolysis in response to plasmin and its cross-linking by factor XIIIa, we studied a new hamster monoclonal antibody (mAb) 7E9 that reacts with the γ chain of mouse fibrinogen. This antibody inhibits platelet adhesion to fibrinogen, platelet-mediated clot retraction, platelet aggregation, and FXIIIa-mediated cross-linking of fibrin; it also facilitates tissue plasminogen activator (tPA)-mediated lysis of fibrin formed either in the absence or presence of platelets. These data provide evidence that the C-terminus of mouse fibrinogen γ chain, like that of human fibrinogen, is involved in fibrinogen binding to platelets and FXIIIa-mediated cross-linking of fibrin. Our data raise the possibility that a therapeutic agent that targets the C-terminus of the γ chain in human fibrinogen might have broad antithrombotic and profibrinolytic effects.

Keywords

Fibrinogen - thrombolysis - factor XIIIa - antithrombotic therapy

Full Text

References

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