中文摘要：黄曲霉分泌的黄曲霉毒素，可以定植于呼吸道从而引发真菌性鼻窦炎和支气管肺曲霉病。黄曲霉是全球引发扩散性曲霉病的第二大原因。由于很多呼吸道病原体分泌的毒素会损害粘膜免疫功能，因此本研究的目的是探索黄曲霉毒素暴露对呼吸道细胞生理的严重影响。利用气液界面方式对人的鼻腔和支气管细胞进行培养，发现其纤毛摆动频率（CBF）、细胞内游离钙和一氧化氮（NO）。研究发现，由呼吸黄曲霉分泌的黄曲霉毒素会损害呼吸道纤毛的运动和化学感应机能，从而引发真菌性气道疾病。
外文摘要：Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6-12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases.
作者：Lee, RJ；Workman, AD；Carey, RM；等
作者单位：宾夕法尼亚大学佩雷尔曼医学院
期刊名称：SCIENTIFIC REPORTS
期刊影响因子：5.228
出版年份：2016
出版刊次：6
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