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.

Potentiating the cellular targeting and anti-tumor activity of Dp44mTviabinding to human serum albumin: two saturable mechanisms of Dp44mT uptake by cells

“…5B-D ), suggesting competition between the unlabeled and labeled protein for the same binding sites. These results agree with previous studies demonstrating 59 Fe-Tf, 125 I-Tf and 125 I-HSA uptake occur via energy- and temperature-sensitive endocytosis [ 69 , 70 , 74 , 75 ].…”

“…Together, these data indicate in contrast to 59 Fe-Tf, 125 I-Tf and 125 I-HSA uptake by cells, 14 C-Dp44mT uptake in the presence of HSA was insensitive to glucose levels, inhibition of energy metabolism and the suppressive effects of lysosomotropic agents or an endo-/exocytosis inhibitor. These observations suggested the HSA-stimulated mechanism of 14 C-Dp44mT uptake occurred by a different pathway to the uptake of either 125 I-HSA or 59 Fe- 125 I-Tf that occur by endocytosis or endocytosis requiring endosomal acidification, respectively [ 52 , 69 - 71 , 74 , 75 ].…”

HIF1A-dependent induction of alveolar epithelial PFKFB3 dampens acute lung injury

“…The alveolar epithelium is composed of type I and type II alveolar epithelial cells (14),although alveolar type I (AT I) cells comprise a higher percentage of the lung surface area, both cell types are found in similar numbers in the lung (15). Alveolar type II (ATII) cells play a critical part in ALI, which has been established in experimental models of lung insults (16).…”

Nanoparticles of folic acid‐methyl‐β‐cyclodextrin (FA‐MβCD)/adamantane‐albumin exhibit enhanced antitumor activity compared with FA‐MβCD alone

“…The HSA receptors FcRn (neonatal Fc receptor) and SPARC (secreted protein acidic and rich in cysteine) are expressed in KB cells and A549 cells [ 37 , 38 ]. Since the conformation of the Ad‐HSA conjugate is similar to that of HSA (Fig.…”