NDLI: P-glycoprotein (MDR1) functional activity in human alveolar epithelial cell monolayers

Content Provider	Springer Nature Link
Author	Endter, Sibylle Becker, Ulrich Daum, Nicole Huwer, Han Lehr, Claus Michael Gumbleton, Mark Ehrhardt, Carsten
Copyright Year	2006
Abstract	The distribution of the P-glycoprotein (P-gp/MDR1) efflux transporter at mucosal barriers has defined it as a functionally important element in limiting drug absorption into the systemic circulation. However, little is known about the distribution and functionality of P-gp/MDR1 in the human lung. Here, the presence of P-gp/MDR1 was investigated immunohistochemically in distal human lung tissue and at mRNA and protein levels in human alveolar epithelial cells (hAEpC) in primary culture. We studied the presence and activity of P-gp/MDR1 in hAEpC monolayers by Western blotting, by immunofluorescence microscopy and by conducting bi-directional transport studies employing a P-gp substrate (rhodamine 123) with and without a P-gp inhibitor (verapamil). The flux of fluorescein sodium was also examined as a paracellular transport marker. Alveolar tissue specimens showed P-gp localised at the luminal membranes of type I pneumocytes. Reverse transcription-polymerase chain reaction revealed the presence of mRNA encoding for P-gp/MDR1 in freshly isolated (i.e. type II) hAEpC and in monolayers of hAEpC cultured for 8 days (i.e. type I-like morphology). At the protein level, P-gp could be detected in hAEpC monolayers after 8 days in culture but not in freshly isolated type II pneumocytes. The flux of rhodamine 123 across hAEpC monolayers on day 8 in culture exhibited net secretion, which disappeared in the presence of verapamil. Fluorescein sodium fluxes showed no distinct directionality. Our findings indicate that P-gp is functionally active in the human alveolar airspace and that hAEpC monolayers might provide a suitable in vitro model for studying P-gp function mechanistically in the distal human lung.
Starting Page	77
Ending Page	84
Page Count	8
File Format	PDF
ISSN	0302766X
Journal	Cell and Tissue Research
Volume Number	328
Issue Number	1
e-ISSN	14320878
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-12-13
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	ABC-transporters Cell culture Alveolar epithelium Pulmonary drug delivery Multi-drug resistance Alveolar epithelial cells Human Molecular Medicine Proteomics Human Genetics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Histology Pathology and Forensic Medicine

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