Polyphosphates form antigenic complexes with platelet factor 4 (PF4) and enhance PF4-binding to bacteria

Sven Brandt; Krystin Krauel; Miriam Jaax; Thomas Renné; Christiane A. Helm; Sven Hammerschmidt; Mihaela Delcea; Andreas Greinacher

doi:10.1160/TH15-01-0062

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(06): 1189-1198
DOI: 10.1160/TH15-01-0062

Cellular Haemostasis and Platelets

Schattauer GmbH

Polyphosphates form antigenic complexes with platelet factor 4 (PF4) and enhance PF4-binding to bacteria

Sven Brandt

¹ZIK HIKE – Centre of innovation competence “Humoral Immune Reactions in Cardiovascular Diseases“, Greifswald, Germany

,

Krystin Krauel

²Institute for Immunology and Transfusion Medicine, Greifswald, Germany

,

Miriam Jaax

²Institute for Immunology and Transfusion Medicine, Greifswald, Germany

,

Thomas Renné

³Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

,

Christiane A. Helm

⁴Institute for Experimental Physics, Greifswald, Germany

,

Sven Hammerschmidt

⁵Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany

,

Mihaela Delcea^*

¹ZIK HIKE – Centre of innovation competence “Humoral Immune Reactions in Cardiovascular Diseases“, Greifswald, Germany

,

Andreas Greinacher^*

²Institute for Immunology and Transfusion Medicine, Greifswald, Germany

› Author Affiliations

Abstract

Summary

Short chain polyphosphates (polyP) are pro-coagulant and pro-inflammatory platelet released inorganic polymers. The platelet chemokine platelet factor 4 (PF4) binds to lipid A on bacteria, inducing an antibody mediated host defense mechanism, which can be misdirected against PF4/heparin complexes leading to the adverse drug reaction heparin-induced thrombocytopenia (HIT). Here, we demonstrate that PF4 complex formation with soluble short chain polyP contributes to host defense mechanisms. Circular dichroism spectroscopy and isothermal titration calorimetry revealed that PF4 changed its structure upon binding to polyP in a similar way as seen in PF4/heparin complexes. Consequently, PF4/polyP complexes exposed neoepitopes to which human anti-PF4/heparin antibodies bound. PolyP enhanced binding of PF4 to Escherichia coli, hereby facilitating bacterial opsonisation and, in the presence of human anti-PF4/polyanion antibodies, phagocytosis. Our study indicates a role of polyP in enhancing PF4-mediated defense mechanisms of innate immunity.

Keywords

Antigen generation - conformational changes - phagocytosis - platelet factor 4 - polyphosphates

Full Text

References

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