Myeloperoxidase attracts neutrophils by physical forces
Myeloperoxidase attracts neutrophils by physical forces
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DOI：
10.1182/blood-2010-05-284513
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发表时间：
2011-01-27
期刊：
影响因子：
20.3
通讯作者：
Baldus, Stephan
中科院分区：
文献类型：
--
作者：
Klinke, Anna;Nussbaum, Claudia;Baldus, Stephan
多形核中性粒细胞（PMN）的募集仍然是先天免疫防御的首要前提，也是炎症性血管疾病的关键共同创始人。中性粒细胞募集包括一系列协同事件，允许白细胞的捕获、粘附和外渗。尽管中性粒细胞的滚动、结合和渗出已被充分表征，但受体介导的过程、减弱白细胞带负电的糖萼和内皮细胞之间静电排斥的机制仍然知之甚少。我们提供了髓过氧化物酶（MPO）的证据，髓过氧化物酶是一种丰富的中性粒细胞衍生的血红素蛋白，通过其正表面电荷促进中性粒细胞募集。在体外，MPO 引起高度定向的 PMN 运动，这完全依赖于与白细胞表面的静电相互作用。在体内，在肝缺血和再灌注模型中、在门静脉内递送 MPO 时以及在暴露于局部炎症或动脉内 MPO 应用的提睾肌中，PMN 募集被证明是 MPO 依赖性的。鉴于 MPO 对内皮细胞和白细胞表面都有亲和力，由于其表面带正电荷，MPO 逐渐成为 PMN 募集的介质。这种静电 MPO 效应不仅展示了该酶迄今为止未被识别的、独立于催化的功能，而且凸显了由物理力驱动的 PMN 吸引的主要机制。 （血。2011；117（4）：1350-1358）
Recruitment of polymorphonuclear neutrophils (PMNs) remains a paramount prerequisite in innate immune defense and a critical cofounder in inflammatory vascular disease. Neutrophil recruitment comprises a cascade of concerted events allowing for capture, adhesion and extravasation of the leukocyte. Whereas PMN rolling, binding, and diapedesis are well characterized, receptor-mediated processes, mechanisms attenuating the electrostatic repulsion between the negatively charged glycocalyx of leukocyte and endothelium remain poorly understood. We provide evidence for myeloperoxidase (MPO), an abundant PMN-derived heme protein, facilitating PMN recruitment by its positive surface charge. In vitro, MPO evoked highly directed PMN motility, which was solely dependent on electrostatic interactions with the leukocyte's surface. In vivo, PMN recruitment was shown to be MPO-dependent in a model of hepatic ischemia and reperfusion, upon intraportal delivery of MPO and in the cremaster muscle exposed to local inflammation or to intraarterial MPO application. Given MPO's affinity to both the endothelial and the leukocyte's surface, MPO evolves as a mediator of PMN recruitment because of its positive surface charge. This electrostatic MPO effect not only displays a so far unrecognized, catalysis-independent function of the enzyme, but also highlights a principal mechanism of PMN attraction driven by physical forces. (Blood. 2011; 117(4):1350-1358)