Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Immunol. 2020 Oct 15;11:551057. doi: 10.3389/fimmu.2020.551057. eCollection 2020.
Neutrophils are the first cells to migrate into the cornea in response to alkali burns, and excessive neutrophil infiltration is associated with inflammatory injury and a poorer prognosis. In an effort to understand the mechanisms underlying the inflammation mediated by neutrophils after alkali burns, we examined the role of alkali-activated neutrophils on human corneal epithelial cells (HCEs) proliferation and migration, as well as the effects of acetylsalicylic acid (ASA) and dexamethasone (DXM) on NETosis. We stimulated human neutrophils with sodium hydroxide (NaOH) and observed dose- and time-dependent neutrophil extracellular traps (NETs) formation. We also observed that ASA, but not DXM, significantly inhibited NaOH-induced NETosis. Furthermore, the activation of nuclear factor (NF)-κB, but not the production of reactive oxygen species, was involved in ASA-regulated NETosis. Moreover, NETs were found to be involved in alkali-activated neutrophils (ANs) induced neutrophil-HCE adhesion. ANs enhanced HCEs proliferation via phagocytosis. Meanwhile, ANs inhibited HCEs migration through the release of NETs, which was partially rescued by 5 mM ASA. In conclusion, ANs may interfere with HCEs proliferation and migration by phagocytosis and NETs formation, respectively. ASA may enhance HCEs migration by decreasing NETs formation through inhibition of NF-κB activation and could be a promising strategy for improving the prognosis of corneal alkali burns.
中性粒细胞是对碱烧伤作出反应而首先迁移到角膜的细胞，过多的中性粒细胞浸润与炎症损伤和预后不良有关。为了了解碱烧伤后中性粒细胞介导的炎症的机制，我们研究了碱激活的中性粒细胞对人角膜上皮细胞（HCE）增殖和迁移的作用，以及乙酰水杨酸（ASA）和地塞米松（DXM）对 NETosis 的影响。我们用氢氧化钠（NaOH）刺激人中性粒细胞，观察到剂量和时间依赖性的中性粒细胞细胞外陷阱（NETs）形成。我们还观察到 ASA 而非 DXM 可显著抑制 NaOH 诱导的 NETosis。此外，NF-κB 的激活而非活性氧的产生参与了 ASA 调节的 NETosis。此外，发现 NETs 参与了碱激活的中性粒细胞（ANs）诱导的中性粒细胞-HCE 黏附。ANs 通过吞噬作用增强 HCEs 的增殖。同时，ANs 通过释放 NETs 抑制 HCEs 的迁移，而 5mM ASA 可部分挽救这一作用。总之，ANs 可能分别通过吞噬作用和 NETs 形成来干扰 HCEs 的增殖和迁移。ASA 可能通过抑制 NF-κB 激活减少 NETs 的形成来增强 HCEs 的迁移，这可能是改善角膜碱烧伤预后的有前途的策略。
