Document Detail


Enhancing effect of poly(amino acid)s on albumin uptake in human lung epithelial A549 cells.
MedLine Citation:
PMID:  23719965     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
  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.
Authors:
Ryoko Yumoto; Sayuri Suzuka; Saori Nishimoto; Junya Nagai; Mikihisa Takano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-5-28
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  -     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-5-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical & Health Sciences, Hiroshima University.
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