Posted by Alveolar epithelial type II (AT2) cells secrete pulmonary surfactant via lamellar bodies (LBs). Abnormalities in LBs are associated with pulmonary disorders, including fibrosis. However, high-content screening (HCS) for LB abnormalities is limited by the lack of understanding of AT2 cell functions. In the present study [1] , LB cells harboring LB-like organelles that secrete surfactant proteins were developed. These cells were more similar to AT2 cells than to parental A549 cells. LB cells recapitulated amiodarone (AMD)-induced LB enlargement, similar to AT2 cells of patients exposed to AMD. To reverse AMD-induced LB abnormalities, HCS of approved drugs was performed and 2-hydroxypropyl-β-cyclodextrin (HPβCD) was identified as a potential therapeutic agent. A transcriptome analysis revealed that HPβCD modulates lipid homeostasis. In addition, HPβCD inhibited AMD-induced LB abnormalities in human induced pluripotent stem cell–derived AT2 cells. The results demonstrate that LB cells are useful for HCS and suggest that HPβCD is a candidate therapeutic agent for AMD-induced interstitial pneumonia.
[1] Shuhei Kanagaki, Takahiro Suezawa, Keita Moriguchi, Kazuhisa Nakao, Masayasu Toyomoto, Yuki Yamamoto, Koji Murakami, Masatoshi Hagiwara, and Shimpei Gotoh (2021) Hydroxypropyl Cyclodextrin Improves Amiodarone-induced Aberrant Lipid Homeostasis of Alveolar Cells. American Journal of Respiratory Cell and Molecular Biology 64,
https://doi.org/10.1165/rcmb.2020-0119OC
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