2013年12月
Enhancing Effect of Poly(amino acid)s on Albumin Uptake in Human Lung Epithelial A549 Cells
DRUG METABOLISM AND PHARMACOKINETICS
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- 巻
- 28
- 号
- 6
- 開始ページ
- 497
- 終了ページ
- 503
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.2133/dmpk.DMPK-13-RG-028
- 出版者・発行元
- JAPANESE SOC STUDY XENOBIOTICS
The clearance of albumin from the alveolar space is a critical process in the recovery from edema. In this study, we investigated the effect of poly(amino acid)s such as poly-L-ornithine (PLO) on albumin uptake in the cultured lung epithelial cell line A549. FITC-albumin uptake as well as cell surface binding was markedly stimulated by co-incubation with PLO, and there was a good correlation between them. After being taken up by A549 cells, FITC-albumin was predominantly targeted to lysosomes. Interestingly, pretreatment of A549 cells with PLO further stimulated FITC-albumin uptake, even in the absence of PLO in the uptake buffer. FITC-albumin uptake in the presence of PLO was inhibited by a metabolic inhibitor, clathrin-mediated endocytosis inhibitors, and a macropinocytosis inhibitor, indicating the involvement of clathrin-mediated endocytosis and/or macropinocytosis. The effect of PLO on FITC-albumin clearance was also examined in an in vivo pulmonary administration method in rats, and coadministration of PLO enhanced fluorescence elimination from the lungs. These findings suggest that pulmonary administration of poly(amino acid)s such as PLO is a possible strategy for enhancing albumin clearance from the alveolar space, and thereby facilitating the recovery from pulmonary edema.
- リンク情報
- ID情報
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- DOI : 10.2133/dmpk.DMPK-13-RG-028
- ISSN : 1347-4367
- eISSN : 1880-0920
- Web of Science ID : WOS:000328312300008