Department of Vascular Surgery, Affiliated Hospital of Chengde Medical University, No. 36, Nanyingzi Street, Shuangqiao District, Chengde, Hebei 067000, China.
Laboratory Medicine, Affiliated Hospital of Chengde Medical University, No. 36, Nanyingzi Street, Shuangqiao District, Chengde, Hebei 067000, China.
Biosci Rep. 2020 Sep 30;40(9). doi: 10.1042/BSR20200928.
Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute systemic vasculitis syndrome that mainly occurs in infants under 5 years of age. In the current manuscript, we were aiming to analyze the role of neutrophil extracellular traps (NETs) in the pathogenesis of KD, especially their interplay with peripheral blood mononuclear cells (PBMCs). Neutrophils were exposed to 20 nM phorbol myristate acetate (PMA), we found that neutrophils of KD patients were more likely to form NETs compared with healthy controls (HCs). Furthermore, PBMCs were cultured with NETs for 24 h, and we observed that NETs significantly increased the cell viability, suppressed cell apoptosis, and enhanced the pro-inflammatory cytokines production and NF-κB activation in PBMCs from KD patients. In addition, with the stimulation of NETs, the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were increased, which were related with the pathological mechanism of KD. At last, we examined the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling, and we found NETs treatment obviously enhanced the activation of PI3K and Akt. In conclusion, these findings suggested that the formation of NETs may alter the biologic responses of PBMC and affect the vascular injury in KD.
川崎病（KD），又称黏膜皮肤淋巴结综合征，是一种主要发生于 5 岁以下婴幼儿的急性全身性脉管炎综合征。在本手稿中，我们旨在分析中性粒细胞胞外陷阱（NETs）在 KD 发病机制中的作用，特别是它们与外周血单核细胞（PBMCs）的相互作用。我们将中性粒细胞暴露于 20 nM 佛波醇肉豆蔻酸酯（PMA）中，发现与健康对照组（HCs）相比，KD 患者的中性粒细胞更容易形成 NETs。此外，我们用 NETs 培养 PBMCs 24 小时，观察到 NETs 显著增加了 KD 患者 PBMCs 的细胞活力，抑制了细胞凋亡，并增强了促炎细胞因子的产生和 NF-κB 的激活。此外，随着 NETs 的刺激，血管内皮生长因子 A（VEGF-A）和缺氧诱导因子-1α（HIF-1α）的表达增加，这与 KD 的病理机制有关。最后，我们检测了磷酸肌醇 3 激酶（PI3K）/Akt 信号的激活，发现 NETs 处理明显增强了 PI3K 和 Akt 的激活。总之，这些发现表明 NETs 的形成可能改变 PBMC 的生物学反应，并影响 KD 中的血管损伤。
