Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Thromb Haemost. 2021 Aug;121(8):1021-1030. doi: 10.1055/a-1336-0526. Epub 2021 Feb 16.
Neutrophil extracellular traps (NETs) and polyphosphates (polyP) have been recognized as procoagulant polyanions. This review summarizes the activities and regulation of the two procoagulant mediators and compares their functions. NETs are composed of DNA which like polyP is built of phosphate units linked by high-energy phosphoanhydride bonds. Both NETs and polyP form insoluble particulate surfaces composed of a DNA/histone meshwork or Ca-rich nanoparticles, respectively. These polyanionic molecules modulate coagulation involving an array of mechanisms and trigger thrombosis via activation of the factor XII-driven procoagulant and proinflammatory contact pathway. Here, we outline the current knowledge on NETs and polyP with respect to their procoagulant and prothrombotic nature, strategies for interference of their activities in circulation, as well as the crosstalk between these two molecules. A better understanding of the underlying, cellular mechanisms will shed light on the therapeutic potential of targeting NETs and polyP in coagulation and thrombosis.
中性粒细胞胞外诱捕网（NETs）和多聚磷酸盐（polyP）已被认为是促凝聚阴离子。本综述总结了这两种促凝介质的活性和调节，并比较了它们的功能。NETs 由 DNA 组成，与 polyP 一样，由通过高能磷酸酐键连接的磷酸盐单元组成。NETs 和 polyP 分别形成由 DNA/组蛋白网格或富含 Ca 的纳米颗粒组成的不溶性颗粒表面。这些阴离子分子通过一系列机制调节凝血，并通过激活因子 XII 驱动的促凝和促炎接触途径引发血栓形成。在这里，我们概述了有关 NETs 和 polyP 的最新知识，包括它们的促凝和促血栓形成特性、干扰其在循环中活性的策略，以及这两种分子之间的串扰。对潜在细胞机制的更好理解将揭示靶向 NETs 和 polyP 在凝血和血栓形成中的治疗潜力。
