title: Enhancing effect of poly(amino acid)s on albumin uptake in human lung epithelial A549 cells.
abstract: 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 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 thereby facilitating the recovery from pulmonary edema.
authors.affiliation: Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical & Health Sciences, Hiroshima University.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yumoto
authors.forename: Sayuri
authors.initials: S
authors.lastname: Suzuka
authors.forename: Saori
authors.initials: S
authors.lastname: Nishimoto
authors.forename: Junya
authors.initials: J
authors.lastname: Nagai
authors.forename: Mikihisa
authors.initials: M
authors.lastname: Takano
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010873:Pinocytosis; D011650:Pulmonary Alveoli / Q000166:cytology*; D011654:Pulmonary Edema / Q000503:physiopathology; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: C518288:FITC-albumin; D010455:Peptides; D012709:Serum Albumin; C008973:polyornithine; D016650:Fluorescein-5-isothiocyanate