Am J Physiol Lung Cell Mol Physiol 285: L869-L878, 2003.
First published August 8, 2003; doi:10.1152/ajplung.00077.2003
1040-0605/03 $5.00
Identification and characterization of rodent ABCA1 in isolated type II pneumocytes
Anna E. Bortnick,1,*
Elda Favari,2,*
Jian-Qin Tao,3
Omar L. Francone,4
Muredach Reilly,5
Yuzhen Zhang,5
George H. Rothblat,1 and
Sandra R. Bates3
1Children's Hospital of Philadelphia, 5University of Pennsylvania Medical Center, and 3Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; 2Institute of Pharmacological and Biological Sciences, University of Parma, Parma, Italy; and 4Pfizer, Incorporated, Groton, Connecticut 06340
Submitted 17 March 2003
; accepted in final form 9 June 2003
ATP-binding cassette transporter A1 (ABCA1) promotes transfer of cholesterol and phospholipid from cells to lipid-free serum apolipoproteins. ABCA1 mRNA and protein expression in primary cultures of rodent type II cells was sensitive to upregulation with 5 µM9-cis-retinoic acid (9cRA) and 6.2 µM 22-hydroxycholesterol (22-OH). The increase in ABCA1 protein levels was time dependent and was maximal after 16 h of exposure to 9cRA + 22-OH. Inducible ABCA1 was also found in transformed cell lines of lung origin: WI38/VA13, A549, and NIH-H441 cells. Stimulation of ABCA1 in rat type II cells by 9cRA + 22-OH resulted in a four- or fivefold enhancement of efflux of radioactive phospholipid or cholesterol, respectively, from the pneumocytes to apolipoprotein AI (apo AI), whereas cAMP (0.3 mM) had no effect. ABCA1-mediated lipid efflux to apo AI was independent of the surfactant secretion pathway, inasmuch as upregulation of ABCA1 resulted in a reduction of secretagogue-stimulated surfactant phospholipid release. These studies demonstrate the presence of functional ABCA1 in type II cells from the lung.
phospholipid; cholesterol; lung; reverse cholesterol transport; surfactant secretion
Address for reprint requests and other correspondence: S. R. Bates, Institute for Environmental Medicine, University of Pennsylvania, 1 John Morgan Bldg., 36th and Hamilton Walk, Philadelphia, PA 19104-6068 (E-mail: batekenn{at}mail.med.upenn.edu).
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Copyright © 2003 by the American Physiological Society.
