[Transport of proteins and peptides across human cultured alveolar A549 cell monolayers].
OBJECTIVE
An in vitro cultured monolayer system of alveolar epithelial cells was used as a model to investigate the transport pathway peptides or proteins, salmon calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant human growth hormone (rhGH), in pulmonary epithelium in vivo.


METHODS
Human lung adenocarcinoma A549 cells formed continuous monolayers with growing polycarbonate filters of Transwell plate. Transport studies of macromolecules in the monolayer system were carried out after 6 days in culture. The transport of peptides or proteins with MW 3,400 - 22,000 was studied in cultured human lung adenocarcinoma A549 cell monolayers at different conditions.


RESULTS
The results showed that the apparent permeability coefficients (Papp) of these macromolecules across A549 cell monolayers ranged from 2 x 10(-6) to 5 x 10(-6) cm x s(-1) and exhibited good inverse correlation with molecule weight. No concentration, direction and temperature dependence were observed in the permeation of sCT, INS and rHAV2. While the Papp of rhGH in the BA direction (2.25 x 10(-6) cm x s(-1)) was significantly less than that in the reverse direction. The Papp values of rhGH were concentration and temperature independent in the AB direction.


CONCLUSIONS
These findings suggest that the hydrophilic peptides and proteins, salmon calcitonin, insulin, recombinant hirudin, and recombinant human growth hormone used in this study, appeared to penetrate the A549 cell monolayers via a paracellular pathway by passive diffusion mechanism.
Wang
Zhi-ying
ZY
Department of Pharmaceutics, Peking University Health Science Center, Beijing, China.
Zhang
Yue
Y
Zhang
Qiang
Q
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D002116:Calcitonin / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D006629:Hirudins / Q000493:pharmacokinetics; D019382:Human Growth Hormone / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000493:pharmacokinetics*; D010539:Permeability; D011506:Proteins / Q000493:pharmacokinetics*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology
D006629:Hirudins; D007328:Insulin; D010455:Peptides; D011506:Proteins; D019382:Human Growth Hormone; C028815:salmon calcitonin; D002116:Calcitonin