Neutrophil Extracelluar Traps Stimulate Proinflammatory Response in Human Airway Epithelial cells
Neutrophil Extracelluar Traps Stimulate Proinflammatory Response in Human Airway Epithelial cells
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DOI：
10.1159/000460293
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发表时间：
2017-01-01
影响因子：
5.3
通讯作者：
Trevani, Analia S.
中科院分区：
文献类型：
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作者：
Sabbione, Florencia;Keitelman, Irene A.;Trevani, Analia S.
组织损伤导致尿酸(UA)的释放。在较高的局部浓度下，尿酸可形成尿酸单钠晶体(MSU)。MSU和UA刺激中性粒细胞释放额外的细胞陷阱(NET)。在这里，我们研究了这些网络是否可能通过刺激呼吸道上皮细胞释放细胞因子而参与炎症的发展。我们发现Net能显著增加肺泡和支气管上皮细胞分泌CXCL8/IL-8和IL-6。当二苯碘、弹性酶抑制剂或异硫氰胺抑制NETase时，未观察到上述作用。用香烟烟雾提取物诱导的净致炎能力也得到了类似的发现，表明净促炎症能力与诱导刺激无关。此外，Net既不影响上皮细胞的活性和形态，也不影响极化细胞的屏障完整性。微球菌核酸酶降解DNA、肝素处理或抑制固定在DNA上的弹性蛋白酶不影响Net的内皮刺激能力，但经抗HMGB-1封闭抗体预处理后，Net的刺激能力显著降低。综上所述，我们的发现表明，NET对呼吸道上皮细胞具有直接的促炎作用，这可能在体内有助于中性粒细胞的进一步募集和肺组织损伤的炎症持续。(C)2017年S.Karger AG，巴塞尔。
Tissue injury leads to the release of uric acid (UA). At high local concentrations, UA can form monosodium urate crystals (MSU). MSU and UA stimulate neutrophils to release extra cellular traps (NET). Here, we investigated whether these NET could be involved in the development of inflammation by stimulating cytokine release by airway epithelial cells. We found that NET significantly increased the secretion of CXCL8/IL-8 and IL-6 by alveolar and bronchial epithelial cells. These effects were not observed when NETosis was inhibited by Diphenyleneiodonium, elastase inhibitor, or CI-amidine. Similar findings were made with NET induced by cigarette smoke extract, suggesting that NET proinflammatory capacity is independent of the inducing stimulus. Furthermore, NET affected neither the viability and morphology of epithelial cells nor the barrier integrity of polarized cells. The epi-thelial stimulatory capacity of NET was not affected by degradation of DNA with micrococcal nuclease, treatment with heparin, or inhibition of the elastase immobilized to DNA, but it was significantly reduced by pretreatment with an anti-HMGB-1 blocking antibody. Altogether, our findings indicate that NET exert direct proinflammatory effects on airway epithelial cells that might contribute in vivo to the further recruitment of neutrophils and the perpetuation of inflammation upon lung tissue damage. (C) 2017 S. Karger AG, Basel.