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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
1   ZIK HIKE – Centre of innovation competence “Humoral Immune Reactions in Cardiovascular Diseases“, Greifswald, Germany
,
Krystin Krauel
2   Institute for Immunology and Transfusion Medicine, Greifswald, Germany
,
Miriam Jaax
2   Institute for Immunology and Transfusion Medicine, Greifswald, Germany
,
Thomas Renné
3   Institute 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
4   Institute for Experimental Physics, Greifswald, Germany
,
Sven Hammerschmidt
5   Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany
,
Mihaela Delcea   *
1   ZIK HIKE – Centre of innovation competence “Humoral Immune Reactions in Cardiovascular Diseases“, Greifswald, Germany
,
Andreas Greinacher   *
2   Institute for Immunology and Transfusion Medicine, Greifswald, Germany
› Author Affiliations
Further Information

Publication History

Received: 21 January 2015

Accepted after major revision: 17 June 2015

Publication Date:
30 November 2017 (online)

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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

* Shared senior authorship.


 

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