马克斯·普朗克分子生理学研究所Arturo Zychlinsky小组的一项最新研究探明了髓过氧化物酶将染色质转化为中性粒细胞胞外陷阱。相关论文于2025年9月17日发表在《自然》杂志上。

在这里，该课题组人员展示了髓过氧化物酶（MPO），一种高度表达的中性粒细胞蛋白，如何分解核小体，从而促进NET的形成，同时也稳定地与细胞外的NET结合。该研究团队描述了MPO的寡聚状态如何控制这两种结果。MPO二聚体与一个原聚体的核小体DNA相互作用，同时与另一个原聚体停靠在核小体的酸性斑块上。结果，二聚体MPO从核心复合体中取代DNA，最终导致核小体解体。另一方面，MPO单体稳定地与核小体酸性斑块相互作用，而不产生伴随的DNA接触，这解释了MPO单体如何结合并允许NETs在细胞外空间产生次卤代酸。他们的数据表明，MPO与染色质的结合是由特定的分子相互作用控制的，这种相互作用将染色质转化为非复制、非编码状态，以无细胞的方式提供新的生物学功能。据他们所知，该研究团队认为MPO是一类将染色质转化为免疫效应物的蛋白质的第一个成员。

据了解，中性粒细胞是最丰富的生物毒性免疫细胞，将核DNA挤出细胞外空间以维持体内平衡。这些被称为中性粒细胞胞外陷阱（NETs）的蛋白修饰和去致密的细胞外DNA支架控制感染，并参与凝血、自身免疫和癌症。

附：英文原文

Title: Myeloperoxidase transforms chromatin into neutrophil extracellular traps

Author: Burn, Garth Lawrence, Raisch, Tobias, Tacke, Sebastian, Winkler, Moritz, Prumbaum, Daniel, Thee, Stephanie, Gimber, Niclas, Raunser, Stefan, Zychlinsky, Arturo

Issue&Volume: 2025-09-17

Abstract: Neutrophils, the most abundant and biotoxic immune cells, extrude nuclear DNA into the extracellular space to maintain homeostasis. Termed neutrophil extracellular traps (NETs), these protein-modified and decondensed extracellular DNA scaffolds control infection and are involved in coagulation, autoimmunity and cancer1,2. Here we show how myeloperoxidase (MPO), a highly expressed neutrophil protein, disassembles nucleosomes, thereby facilitating NET formation, yet also binds stably to NETs extracellularly. We describe how the oligomeric status of MPO governs both outcomes. MPO dimers interact with nucleosomal DNA using one protomer and concurrently dock into the nucleosome acidic patch with the other protomer. As a consequence, dimeric MPO displaces DNA from the core complex, culminating in nucleosome disassembly. On the other hand, MPO monomers stably interact with the nucleosome acidic patch without making concomitant DNA contacts, explaining how monomeric MPO binds to and licences NETs to confer hypohalous acid production in the extracellular space3. Our data demonstrate that the binding of MPO to chromatin is governed by specific molecular interactions that transform chromatin into a non-replicative, non-encoding state that offers new biological functions in a cell-free manner. We propose that MPO is, to our knowledge, the first member of a class of proteins that convert chromatin into an immune effector.

DOI: 10.1038/s41586-025-09523-9

Source: https://www.nature.com/articles/s41586-025-09523-9