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

被引:40
作者
Brandt, Sven [1 ]
Krauel, Krystin [2 ]
Jaax, Miriam [2 ]
Renne, Thomas [3 ,4 ]
Helm, Christiane A. [5 ]
Hammerschmidt, Sven [6 ]
Delcea, Mihaela [1 ]
Greinacher, Andreas [2 ]
机构
[1] Ernst Moritz Arndt Univ Greifswald, ZIK HIKE Ctr Innovat Competence Humoral Immune Re, D-17489 Greifswald, Germany
[2] Inst Immunol & Transfus Med, D-17475 Greifswald, Germany
[3] Univ Hosp Hamburg Eppendorf, Inst Clin Chem & Lab Med, Hamburg, Germany
[4] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden
[5] Inst Expt Phys, Greifswald, Germany
[6] Interfac Inst Genet & Funct Genom, Dept Genet Microorganisms, Greifswald, Germany
关键词
Antigen generation; conformational changes; phagocytosis; platelet factor 4; polyphosphates; HEPARIN-INDUCED THROMBOCYTOPENIA; ISOTHERMAL TITRATION CALORIMETRY; CIRCULAR-DICHROISM SPECTRA; HERMANSKY-PUDLAK SYNDROME; ANTI-PF4/HEPARIN ANTIBODIES; PLATELET POLYPHOSPHATES; INORGANIC POLYPHOSPHATE; CONFORMATIONAL-CHANGES; BETA-LACTOGLOBULIN; IN-VITRO;
D O I
10.1160/TH15-01-0062
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1189 / 1198
页数:10
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