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Originally published as JHC exPRESS on September 18, 2006.
doi:10.1369/jhc.6A6962.2006
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Journal of Histochemistry and Cytochemistry
Volume 55 (1): 71-83, 2007
Copyright ©The Histochemical Society, Inc.

Expression of ABCA3 in Developing Lung and Other Tissues

Mildred T. Stahlman, Valérie Besnard, Susan E. Wert, Timothy E. Weaver, Sharon Dingle, Yan Xu, Kara von Zychlin, Sandra J. Olson and Jeffrey A. Whitsett

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and The University of Cincinnati College of Medicine, Cincinnati, Ohio (TEW,SEW,VB,YX,KVZ,SD,JAW), and Divisions of Neonatology (MTS) and Pathology (SJO), Vanderbilt University School of Medicine, Nashville, Tennessee

Correspondence to: Jeffrey A. Whitsett, MD, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. E-mail: jeff.whitsett{at}cchmc.org

ABCA3 is a member of the ATP-binding cassette (ABC) family of transport proteins and is required for perinatal respiratory adaptation. Monoclonal and polyclonal antibodies were generated against a recombinant human ABCA3 peptide and used to assess its expression in the developing lung and adult tissues. Immunostaining for ABCA3 was detected at highest levels in type II epithelial cells of the lung but was also noted in other organs including liver, stomach, kidney, adrenal, pancreas, trachea, and brain. In the fetal lung, ABCA3 staining and mRNA increased prior to birth. Like other surfactant protein genes, ABCA3 expression was induced by thyroid transcription factor-1 in vitro. ABCA3 was coexpressed with SP-B and proSP-C in type II epithelial cells. ABCA3 staining was detected surrounding large, intracellular organelles consistent with its association with lamellar bodies. In the human fetal lung, ABCA3 staining was not detected prior to 22–23 weeks of gestation, except in the presence of pulmonary inflammation. ABCA3 was detected in type II epithelial cells of the human lung from 28 weeks of gestation and thereafter. Postnatally, intense ABCA3 staining was observed in hyperplastic epithelial cells relining injured airways in infants with chronic lung disease. Localization and regulation of ABCA3 in the respiratory epithelium is consistent with its proposed role in surfactant homeostasis. The role of ABCA3 in extrapulmonary tissues and organs remains to be elucidated. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 55:71–83, 2007)

Key Words: ABC transporters • pulmonary surfactant • lamellar body • bronchopulmonary dysplasia • thyroid transcription factor 1 • immunohistochemistry


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