Cigarette smoke total particulate matter increases mucous secreting cell numbers in vitro: A potential model of goblet cell hyperplasia

Cigarette smoke total particulate matter increases mucous secreting cell numbers in vitro: A potential model of goblet cell hyperplasia
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DOI:
10.1016/j.tiv.2009.12.019
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发表时间:
2010-04-01
影响因子:
3.2
通讯作者:
Gaca, Marianna D.
Gaca, Marianna D.
中科院分区:
医学3区
文献类型:
--
作者:
Haswell, Linsey E.;Hewitt, Katherine;Gaca, Marianna D.

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吸烟与慢性阻塞性肺疾病(COPD)有关,COPD是一个包括慢性肺部炎症、慢性支气管炎和肺气肿的术语。杯状细胞增生是COPD患者中肺上皮的特征性特征,其导致气道粘液(包括粘蛋白MUC 5AC)的过度产生。利用体外分化的肺上皮细胞模型,我们研究了白细胞介素(IL)-13(IL-13)对肺上皮细胞形态和细胞的影响(2.5-20 ng/ml),卷烟烟气总颗粒物(TPM; 0.31-20 μ g/ml)和三种主流香烟烟雾成分:丙烯醛、甲醛和乙醛(均为0.001-1 μ M)(周一至周五每天更换试剂)。对照培养的人支气管上皮细胞(HBECs)进行粘液纤毛分化产生的柱状上皮含有杯状,纤毛和基底细胞。非细胞毒性剂量的IL-13诱导MUC 5AC阳性细胞百分比的显著增加。使用流式细胞术和免疫细胞化学技术鉴定MUC 5AC阳性细胞,TPM处理诱导MUC 5AC阳性细胞的增加,在5 μ g/ml时达到最大。丙烯醛处理也增加了MUC 5AC阳性细胞的百分比。然而,甲醛或乙醛几乎没有影响。这项研究表明,肺毒物可以诱导细胞分化的人肺上皮细胞在体外模型的深刻影响。(C)2010爱思唯尔有限公司版权所有。
Cigarette smoking is associated with chronic obstructive pulmonary disease (COPD) - a term encompassing chronic lung inflammation, chronic bronchitis and emphysema. Goblet cell hyperplasia is a characteristic feature of the lung epithelium in COPD patients contributing to the overproduction of airway mucus, including mucin MUC5AC. Using an in vitro model of differentiated lung epithelium we have investigated morphological and cellular changes in response to interleukin (IL)-13 (2.5-20 ng/ml), cigarette smoke total particulate matter (TPM; 0.31-20 mu g/ml) and three mainstream cigarette smoke constituents: acrolein, formaldehyde and acetaldehyde (all at 0.001-1 mu M) over 28 days during differentiation (agents replaced daily Monday-Friday). Control cultures of human bronchial epithelial cells (HBECs) underwent mucociliary differentiation producing a columnar epithelium containing goblet, ciliated and basal cells. Non-cytotoxic doses of IL-13 induced a significant increase in the percentage of MUC5AC positive cells. Using both flow cytometry and immunocytochemical techniques for identification of MUC5AC positive cells, TPM treatment induced an increase in MUC5AC positive cells, becoming maximal at 5 mu g/ml. Acrolein treatment also increased the percentage of MUC5AC positive cells. However, formaldehyde or acetaldehyde had little effect. This study demonstrates that lung toxicants can induce a profound effect on cellular differentiation in an in vitro model of the human lung epithelium. (C) 2010 Elsevier Ltd. All rights reserved.