Group B streptococcus isolates from septic patients and healthy carriers differentially activate platelet signaling cascades

Celine Siauw; Anna Kobsar; Catharina Dornieden; Claudia Beyrich; Birgitta Schinke; Alexandra Schubert-Unkmeir; Marianne Abele-Horn; Christian P. Speer; Martin Eigenthaler

doi:10.1160/TH05-08-0534

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2006; 95(05): 836-849
DOI: 10.1160/TH05-08-0534

Wound Healing and Inflammation/Infection

Schattauer GmbH

Group B streptococcus isolates from septic patients and healthy carriers differentially activate platelet signaling cascades

Celine Siauw^*

¹University Children’s Hospital, University of Wuerzburg, Wuerzburg, Germany

,

Anna Kobsar^*

³Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany

,

Catharina Dornieden

³Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany

,

Claudia Beyrich

³Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany

,

Birgitta Schinke

³Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany

,

Alexandra Schubert-Unkmeir

²Institute of Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany

,

Marianne Abele-Horn

²Institute of Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany

,

Christian P. Speer

¹University Children’s Hospital, University of Wuerzburg, Wuerzburg, Germany

,

Martin Eigenthaler

³Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany

› Institutsangaben

Abstract

Summary

Infection with group B streptococcus (GBS) is the most common cause of early onset neonatal sepsis in many countries, leading to neonatal morbidity and mortality.There is much evidence fora direct involvement of platelets in the pathogenesis of inflammation and sepsis. Several bacteria are known to directly interact with platelets leading to activation and aggregation,a phenomenon also observed with GBS. Here, we demonstrate that GBS rapidly bound to platelets; however, only strains isolated from septic patients bound fibrinogen on their surface and induced platelet thromboxane synthesis, platelet aggregation, and P-selectin (CD62P) expression. In contrast, GBS strains isolated from healthy newborns or healthy pregnant women induced only shape change, but not platelet thromboxane synthesis, platelet aggregation, or CD62P expression. All GBS strains investigated were able to activate FcγRIIA receptor signaling pathways including phospholipase C gamma2 (PLCγ2), as well as calcium/calmodulin-dependent myosin kinase II (CaMKII) and phosphorylation of myosin light chain (MLC). In contrast, protein kinase C (PKC) was exclusively activated by GBS strains isolated from septic patients, and p38 mitogen activated protein kinase (p38 MAP kinase) was preferentially activated by septic GBS strains. Furthermore, stress signaling kinase SEK1/MKK4 and focal adhesion kinase (FAK) were activated by all tested GBS strains in a FcγRIIA-independent way.This study demonstrates that septic, but not colonizing, GBS strains bind fibrinogen on their surface, and that septic GBS strains influence platelet function not only via the FcγRIIA receptor, but also via pathways distinct from IgG-mediated signalling. These mechanisms lead to platelet aggregation and secretion, thereby possibly modulating the pathophysiologic course of GBS infections.

Keywords

GroupB streptococcus - platelets - FcγRIIA - MAPK - PKC

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Referenzen

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