Active but inoperable thrombin is accumulated in a plasma protein layer surrounding Streptococcus pyogenes

Clément Naudin; Sinead M. Hurley; Erik Malmström; Tom Plug; Oonagh Shannon; Joost C.M. Meijers; Matthias Mörgelin; Lars Björck; Heiko Herwald

doi:10.1160/TH15-02-0127

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 114(04): 717-726
DOI: 10.1160/TH15-02-0127

Blood Cells, Inflammation and Infection

Schattauer GmbH

Active but inoperable thrombin is accumulated in a plasma protein layer surrounding Streptococcus pyogenes

Clément Naudin

¹Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

,

Sinead M. Hurley

¹Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

,

Erik Malmström

¹Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

,

Tom Plug

²Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Oonagh Shannon

¹Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

,

Joost C.M. Meijers

²Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

³Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands

,

Matthias Mörgelin

¹Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

,

Lars Björck

¹Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

,

Heiko Herwald

¹Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden

› Institutsangaben

Abstract

Summary

Activation of thrombin is a critical determinant in many physiological and pathological processes including haemostasis and inflammation. Under physiological conditions many of these functions are involved in wound healing or eradication of an invading pathogen. However, when activated systemically, thrombin can contribute to severe and life-threatening conditions by causing complications such as multiple multi-organ failure and disseminated intravascular coagulation. In the present study we investigated how the activity of thrombin is modulated when it is bound to the surface of Streptococcus pyogenes. Our data show that S. pyogenes bacteria become covered with a proteinaceous layer when incubated with human plasma, and that thrombin is a constituent of this layer. Though the coagulation factor is found attached to the bacteria with a functional active site, thrombin has lost its capacity to interact with its natural substrates and inhibitors. Thus, the interaction of bacteria with human plasma renders thrombin completely inoperable at the streptococcal surface. This could represent a host defense mechanism to avoid systemic activation of coagulation which could be otherwise induced when bacteria enter the circulation and cause systemic infection.

Keywords

Thrombin - fibrinogen - proteolysis - coagulation - Streptococcus pyogenes

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Referenzen

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