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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   *
1   University Children’s Hospital, University of Wuerzburg, Wuerzburg, Germany
,
Anna Kobsar   *
3   Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany
,
Catharina Dornieden
3   Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany
,
Claudia Beyrich
3   Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany
,
Birgitta Schinke
3   Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany
,
Alexandra Schubert-Unkmeir
2   Institute of Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany
,
Marianne Abele-Horn
2   Institute of Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany
,
Christian P. Speer
1   University Children’s Hospital, University of Wuerzburg, Wuerzburg, Germany
,
Martin Eigenthaler
3   Institute of Clinical Biochemistry and Pathobiochemistry/ Central Laboratory, University of Wuerzburg, Wuerzburg, Germany
› Author AffiliationsFinancial support: The authors were supported by a grant from the “Interdisziplinäres Zentrum für Klinische Forschung” (IZKF grant A33) of the University of Wuerzburg.
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Publication History

Received 01 August 2005

Accepted after resubmission 25 March 2006

Publication Date:
01 December 2017 (online)

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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

* Both authors contributed equally.