Abstract
ATP Binding Cassette Subfamily A Member 3 (ABCA-3) is a lipid transporter protein highly expressed in type-II alveolar (AT-II) cells. Mutations in ABCA3 can result in severe respiratory disease in infants and children. To study ABCA-3 deficiency in vitro, primary AT-II cells would be the cell culture of choice although sample accessibility is limited. Our aim was to investigate the suitability of primary nasal epithelial cells, as a surrogate culture model for AT-II cells, to study ABCA-3 deficiency. Expression of ABCA3, and surfactant protein genes, SFTPB and SFTPC, was detected in primary nasal epithelial cells but at a significantly lower level than in AT-II cells. ABCA-3, SP-B, and SP-C were detected by immunofluorescence microscopy in primary nasal epithelial cells. However, SP-B and SP-C were undetectable in primary nasal epithelial cells using western blotting. Structurally imperfect lamellar bodies were observed in primary nasal epithelial cells using transmission electron microscopy. Functional assessment of the ABCA-3 protein demonstrated that higher concentrations of doxorubicin reduced cell viability in ABCA-3 deficient nasal epithelial cells compared to controls in an assay-dependent manner. Our results indicate that there may be a role for primary nasal epithelial cell cultures to model ABCA-3 deficiency in vitro, although additional cell culture models that more effectively recapitulate the AT-II phenotype may be required.
Highlights
Adenosine triphosphate binding cassette sub-family A member 3 (ABCA-3) is a membrane-bound, transporter protein highly expressed in AT-II cells in the lung
We demonstrated that ABCA3 was expressed at a transcriptional and protein level in primary nasal epithelial cells, along with other surfactant-related genes SFTPB and SFTPC
These findings suggest the presence of detectable and functional ATP Binding Cassette Subfamily A Member 3 (ABCA-3) in primary nasal epithelial cells, which infers that the cell culture model could potentially be used as a tool to study ABCA-3 deficiency in vitro as a surrogate cell culture model for AT-II cells
Summary
Adenosine triphosphate binding cassette sub-family A member 3 (ABCA-3) is a membrane-bound, transporter protein highly expressed in AT-II cells in the lung. The ABCA-3 protein is present at the limiting membrane of lamellar bodies in AT-II cells and is responsible for the transport of surfactant lipids from the cytoplasm into the lamellar body [1]. The disease, known as ABCA-3 deficiency, is rare and can present either during the neonatal period with respiratory distress or later during infancy and childhood with symptoms associated with diffuse lung disease [4]. Some of the disease heterogeneity seen in ABCA-3 deficiency can be accounted for by the diversity of the individual mutations [7]
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