Interleukin-13-Induced Mucous Metaplasia Increases Susceptibility of Human Airway Epithelium to Rhinovirus Infection
Interleukin-13-Induced Mucous Metaplasia Increases Susceptibility of Human Airway Epithelium to Rhinovirus Infection
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DOI：
10.1165/rcmb.2009-0244oc
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发表时间：
2010-12-01
影响因子：
6.4
通讯作者：
Widdicombe, Jonathan H.
中科院分区：
文献类型：
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作者：
Lachowicz-Scroggins, Marrah E.;Boushey, Homer A.;Widdicombe, Jonathan H.
鼻病毒感染呼吸道上皮是导致哮喘加重的最常见原因。即使在轻度哮喘中，呼吸道上皮也表现为粘液化生，随着疾病的加重而增加。我们以前发现，人类呼吸道上皮鳞状细胞培养显示鼻病毒感染水平比分化良好的纤毛表型培养高出许多倍。在这里，我们测试了粘液化生也与鼻病毒感染水平增加相关的假设。IL-13诱导粘膜上皮化生，使杯状细胞数量增加一倍。在对照(粘液纤毛)和IL-13处理(粘液化生)培养中，杯状细胞优先被鼻病毒感染。IL-13通过增加受感染的杯状细胞数使受感染细胞数增加一倍。此外，IL-13既增加了杯状细胞的成熟度，也增加了杯状细胞被感染的可能性。IL-13对杯状细胞以外的细胞的感染无明显影响。IL-13治疗没有改变鼻病毒受体ICAM-1的水平，IL-13的增殖作用也没有增加感染，因为鼻病毒不与分裂细胞共存。然而，粘液化生的诱导引起了根尖膜结构的改变，显著地降低了根尖表面的整体中和度，增加了根尖表面的整体平坦度。我们的结论是，哮喘的粘液化生增加了呼吸道上皮对鼻病毒感染的易感性，这是因为顶端表面的整体结构发生了变化。
Infection of airway epithelium by rhinovirus is the most common cause of asthma exacerbations. Even in mild asthma, airway epithelium exhibits mucous metaplasia, which increases with increasing severity of the disease. We previously showed that squamous cultures of human airway epithelium manifest rhinoviral infection at levels many times higher than in well-differentiated cultures of amucociliary phenotype. Here we tested the hypothesis that mucous metaplasia is also associated with increased levels of rhinoviral infection. Mucous metaplasia was induced with IL-13, which doubled the numbers of goblet cells. In both control (mucociliary) and IL-13-treated (mucous metaplastic) cultures, goblet cells were preferentially infected by rhinovirus. IL-13 doubled the numbers of infected cells by increasing the numbers of infected goblet cells. Furthermore, IL-13 increased both the maturity of goblet cells and the probability that a goblet cell would be infected. The infection of cells other than goblet cells was unaltered by IL-13. Treatment with IL-13 did not alter the levels of rhinovirus receptor ICAM-1, nor did the proliferative effects of IL-13 enhance infection, because rhinovirus did not colocalize with dividing cells. However, the induction of mucous metaplasia caused changes in the apical membrane structure, notably a marked decrease in overall ciliation, and an increase in the overall flatness of the apical surface. We conclude that mucous metaplasia in asthma increases the susceptibility of airway epithelium to infection by rhinovirus because of changes in the overall architecture of the apical surface.