Université Paris-Saclay, UVSQ, Inserm U1179, END-ICAP, Versailles, France.
Université Paris-Saclay, UVSQ, Inserm U1173, Infection et Inflammation (2I), France.
Eur J Neurosci. 2023 Feb;57(4):692-704. doi: 10.1111/ejn.15902. Epub 2022 Dec 29.
Spinal cord injuries involve a primary injury that can lead to permanent loss of function and a secondary injury associated with pathologic and inflammatory processes. Extracellular traps are extracellular structures expressed by immune cells that are primarily composed of chromatin, granular enzymes and histones. Extracellular traps are known to induce tissue damage when overexpressed and could be associated in the occurrence of secondary damage. In the present study, we used flow cytometry to demonstrate that at 1 day following a C2 spinal cord lateral hemisection in male Swiss mice, resident microglia form vital microglia extracellular traps, and infiltrating neutrophils form vital neutrophil extracellular traps. We also used immunolabelling to show that microglia near the lesion area are most likely to form these microglia extracellular traps. As expected, infiltrating neutrophils are located at the site of injury, though only some of them engage in post-injury extracellular trap formation. We also observed the formation of microglia and neutrophil extracellular traps in our sham animal models of durotomy, but formation was less frequent than following the C2 hemisection. Our results demonstrate for the first time that microglia form extracellular traps in the spinal cord following injury and durotomy. It remains however to determine the exact mechanisms and kinetics of neutrophil and microglia extracellular traps formation following spinal cord injury. This information would allow to better mitigate this inflammatory process that may contribute to secondary injury and to effectively target extracellular traps to improve functional outcomes following spinal cord injury.
脊髓损伤涉及原发性损伤，可导致永久性功能丧失，以及与病理和炎症过程相关的继发性损伤。细胞外陷阱是免疫细胞表达的细胞外结构，主要由染色质、颗粒酶和组蛋白组成。已知细胞外陷阱在过度表达时会引起组织损伤，并且可能与继发性损伤的发生有关。在本研究中，我们使用流式细胞术证明，在雄性瑞士小鼠 C2 脊髓侧半切后 1 天，驻留小胶质细胞形成有活力的小胶质细胞细胞外陷阱，浸润中性粒细胞形成有活力的中性粒细胞细胞外陷阱。我们还使用免疫标记法表明，损伤区域附近的小胶质细胞最有可能形成这些小胶质细胞细胞外陷阱。正如预期的那样，浸润的中性粒细胞位于损伤部位，但只有其中一些参与损伤后细胞外陷阱的形成。我们还在假手术模型的硬脊膜切开术中观察到小胶质细胞和中性粒细胞细胞外陷阱的形成，但形成的频率低于 C2 半切。我们的研究结果首次证明，损伤和硬脊膜切开术后小胶质细胞在脊髓中形成细胞外陷阱。然而，仍需确定脊髓损伤后中性粒细胞和小胶质细胞细胞外陷阱形成的确切机制和动力学。这些信息将有助于更好地减轻可能导致继发性损伤的炎症过程，并有效地靶向细胞外陷阱，以改善脊髓损伤后的功能结果。
