Polyphosphates form antigenic complexes with platelet factor 4 (PF4) and enhance PF4-binding to bacteria
Polyphosphates form antigenic complexes with platelet factor 4 (PF4) and enhance PF4-binding to bacteria
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DOI：
10.1160/th15-01-0062
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发表时间：
2015-12-01
影响因子：
6.7
通讯作者：
Greinacher, Andreas
中科院分区：
文献类型：
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作者：
Brandt, Sven;Krauel, Krystin;Greinacher, Andreas
短链聚磷酸盐（polyP）是促凝血和促炎血小板释放的无机聚合物。血小板趋化因子血小板因子4（PF 4）与细菌上的脂质A结合，诱导抗体介导的宿主防御机制，该机制可被错误导向PF 4/肝素复合物，导致药物不良反应肝素诱导的血小板减少症（HIT）。在这里，我们证明了PF 4复合物的形成与可溶性短链聚P有助于宿主防御机制。圆二色性光谱和等温滴定量热法显示，PF 4改变其结构后，结合到聚P在PF 4/肝素复合物中所看到的类似的方式。因此，PF 4/聚P复合物暴露了人抗PF 4/肝素抗体结合的新表位。PolyP增强PF 4与大肠杆菌的结合，从而促进细菌调理作用，并且在人抗PF 4/聚阴离子抗体存在下促进吞噬作用。我们的研究表明聚P在增强PF 4介导的先天免疫防御机制中的作用。
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.