Aberrant epithelial differentiation by cigarette smoke dysregulates respiratory host defence
Aberrant epithelial differentiation by cigarette smoke dysregulates respiratory host defence
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DOI：
10.1183/13993003.01009-2017
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发表时间：
2018-04-01
影响因子：
24.3
通讯作者：
van der Does, Anne M.
中科院分区：
文献类型：
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作者：
Amatngalim, Gimano D.;Schrumpf, Jasmijn A.;van der Does, Anne M.
目前尚不清楚香烟烟雾诱导的呼吸道重塑如何影响高表达的呼吸道上皮防御蛋白，从而影响粘膜宿主防御。我们在分化良好的原代支气管上皮细胞(PBEC)培养中评估了一组高表达的呼吸道上皮宿主防御蛋白的定位。然后，在气液界面培养PBEC，在分化过程中每天暴露于全烟烟雾中2-3周。随后对基因表达、蛋白水平和上皮细胞标志物进行了评估。此外，还测定了香烟烟雾诱导的戒烟效应的功能活性和持续时间。与对照组相比，腔细胞表达的聚合物免疫球蛋白受体、分泌性白细胞蛋白酶抑制物和长和短PLUNC(腭骨、肺和鼻上皮克隆蛋白)仅限于表达，而香烟烟雾暴露于分化的PBECs导致这些腔细胞限制性呼吸宿主防御蛋白的表达选择性降低。这种表达的降低是由于香烟烟雾损害了上皮细胞的终末分化，并伴随着IgA跨上皮运输和细菌杀灭的显著减少。这些发现揭示了呼吸道上皮细胞分化在呼吸道宿主防御中的重要性，并可能为吸烟者和慢性阻塞性肺疾病患者对呼吸道感染的易感性增加提供另一种解释。
It is currently unknown how cigarette smoke-induced airway remodelling affects highly expressed respiratory epithelial defence proteins and thereby mucosal host defence.Localisation of a selected set of highly expressed respiratory epithelial host defence proteins was assessed in well-differentiated primary bronchial epithelial cell (PBEC) cultures. Next, PBEC were cultured at the air-liquid interface, and during differentiation for 2-3 weeks exposed daily to whole cigarette smoke. Gene expression, protein levels and epithelial cell markers were subsequently assessed. In addition, functional activities and persistence of the cigarette smoke-induced effects upon cessation were determined.Expression of the polymeric immunoglobulin receptor, secretory leukocyte protease inhibitor and long and short PLUNC (palate, lung and nasal epithelium clone protein) was restricted to luminal cells and exposure of differentiating PBECs to cigarette smoke resulted in a selective reduction of the expression of these luminal cell-restricted respiratory host defence proteins compared to controls. This reduced expression was a consequence of cigarette smoke-impaired end-stage differentiation of epithelial cells, and accompanied by a significant decreased transepithelial transport of IgA and bacterial killing.These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and patients with chronic obstructive pulmonary disease to respiratory infections.