Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents
Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents
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DOI：
10.1183/09031936.00029307
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发表时间：
2008-02-01
影响因子：
24.3
通讯作者：
Wouters, E. F. M.
中科院分区：
文献类型：
--
作者：
Haegens, A.;Vernooy, J. H. J.;Wouters, E. F. M.
在广泛的炎症过程中，中性粒细胞经历继发性坏死，导致髓过氧化物酶(MPO)释放，从而可能损害常驻肺细胞。最近的观察表明，MPO具有促炎特性，与其酶活性无关。本研究的目的是研究肺上皮细胞对MPO的内化作用，并探讨MPO对肺上皮细胞氧化应激、DNA损伤和细胞因子产生的影响。MPO蛋白定位于细胞质中。检测HO-1的表达和DNA链断裂。检测IL-8和IL-6的产生，MPO刺激的细胞分析表明细胞中存在MPO。HO-1在MPO刺激后表达增加，在MPO刺激前预充能进一步增加。MPO暴露还可引起DNA链断裂。有趣的是，MPO抑制了肺上皮细胞中IL-8的产生，但不能抑制肺泡上皮细胞中IL-8的产生。髓过氧化物酶的刺激增加了血氧合酶-1的表达和DNA链的断裂，表明髓过氧化物酶对细胞的破坏能力。此外，髓过氧化物酶抑制支气管上皮细胞产生白介素8，表明中性粒细胞募集的负反馈回路。
During extensive inflammation, neutrophils undergo secondary necrosis causing myeloperoxidase (MPO) release that may damage resident lung cells. Recent observations suggest that MPO has pro-inflammatory properties, independent of its enzymatic activity. The aims of the present study were to characterise MPO internalisation by lung epithelial cells and to investigate the effect of MPO on oxidative stress, DNA damage and cytokine production by lung epithelial cells.Human alveolar and bronchial epithelial cells were stimulated with MPO, with or without priming the cells with pro-inflammatory stimuli. MPO protein was detected in the cell cytoplasm. Expression of haernoxygenase (HO)-1 and DNA strand breakage were determined. The production of interleukin (IL)-8 and -6 were measured.Analyses of MPO-stimulated cells demonstrated MPO presence in the cells. HO-1 expression was increased after MPO stimulation and increased further when cells were primed before MPO stimulation. MPO exposure also induced DNA strand breakage. Interestingly, MPO inhibited IL-8 production in bronchial, but not alveolar epithelium.In conclusion, alveolar and bronchial epithelial cells can internalise myeloperoxidase. Stimulation with myeloperoxidase increases haemoxygenase-1 expression and DNA strand breakage, suggesting cell damaging capacity of myeloperoxidase. In addition, myeloperoxidase inhibited interleukin-8 production by bronchial epithelial cells, indicating a negative feedback loop for neutrophil recruitment.