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Enhancing effect of poly(amino acid)s on albumin uptake in human lung epithelial A549 cells.


Drug Metab Pharmacokinet. 2013 May 28;


Authors: Yumoto R, Suzuka S, Nishimoto S, Nagai J, Takano M


Abstract

  The clearance of albumin from the alveolar space is a critical process in recovery from the edema. In this study, we investigated the effect of poly(amino acid)s such as poly-L-ornithine (PLO) on albumin uptake in 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 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 by a macropinocytosis inhibitor, indicating the involvement of clathrin-mediated endocytosis and/or macropinocytosis. Effect of PLO on FITC-albumin clearance was also examined in in vivo pulmonary administration method in rats, and co-administration 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 therefore facilitating the recovery from the pulmonary edema.

PMID: 23719965 [PubMed - as supplied by publisher]