脑边界衍生的 CXCL2 中性粒细胞驱动 NET 形成，并在缺血性中风后损害血管再灌注。
Brain border-derived CXCL2 neutrophils drive NET formation and impair vascular reperfusion following ischemic stroke.
机构信息
Department of Anesthesiology, Clinical Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Key Laboratory of Anesthesiology, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
出版信息
CNS Neurosci Ther. 2024 Aug;30(8):e14916. doi: 10.1111/cns.14916.
BACKGROUND
The brain border compartments harbor a diverse population of immune cells and serve as invasion sites for leukocyte influx into the brain following CNS injury. However, how brain-border myeloid cells affect stroke pathology remains poorly characterized.
METHODS AND RESULTS
Here, we showed that ischemic stroke-induced expansion of CXCL2 neutrophils, which exhibit highly proinflammatory features. We tracked CXCL2 neutrophils in vivo by utilizing a photoconvertible Kik-GR mouse (fluorescent proteins Kikume Green Red, Kik-GR) and found that brain-infiltrating CXCL2 neutrophils following ischemic stroke were mainly derived from the brain border rather than the periphery. We demonstrated that CXCL2 neutralization inhibited the formation and releasing of neutrophil extracellular traps (NETs) from in vitro cultured primary neutrophils. Furthermore, CXCL2-neutralizing antibody treatment reduced brain infarcts and improved vascular reperfusion at day 3 postischemic stroke.
CONCLUSIONS
Collectively, brain border-derived CXCL2 neutrophil expansion may impair vascular reperfusion by releasing NETs following ischemic stroke.
背景
脑边界隔室容纳了多种免疫细胞，是白细胞在中枢神经系统损伤后涌入大脑的入侵部位。然而，脑边界髓样细胞如何影响中风病理仍知之甚少。
方法和结果
在这里，我们表明，缺血性中风诱导 CXCL2 中性粒细胞的扩张，其表现出高度的促炎特征。我们通过利用光转化的 Kik-GR 小鼠（荧光蛋白 Kikume Green Red，Kik-GR）在体内追踪 CXCL2 中性粒细胞，发现缺血性中风后浸润大脑的 CXCL2 中性粒细胞主要来源于脑边界，而不是外周。我们证明，CXCL2 中和抗体抑制了体外培养的原代中性粒细胞形成和释放中性粒细胞胞外诱捕网（NETs）。此外，CXCL2 中和抗体治疗可减少缺血性中风后第 3 天的脑梗死并改善血管再灌注。
结论
总的来说，脑边界衍生的 CXCL2 中性粒细胞扩张可能通过释放缺血性中风后的 NETs 来损害血管再灌注。
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