Human Adenovirus Modulates Surfactant Phospholipid Trafficking
| Autor: | Rama K. Mallampalli, Diann M. McCoy, Lei Shi, Olga L. Miakotina, Dwight C. Look |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Small interfering RNA
Time Factors medicine.disease_cause Models Biological Biochemistry Adenoviridae Cell Line Gene product Alveolar cells Mice Surface-Active Agents chemistry.chemical_compound Adenosine Triphosphate Structural Biology Phosphatidylcholine Genetics medicine Animals Humans Secretion Molecular Biology Phospholipids Dose-Response Relationship Drug biology Epithelial Cells Cell Biology Fibroblasts Molecular biology Up-Regulation Cell biology Mice Inbred C57BL ATP Binding Cassette Transporter 1 medicine.anatomical_structure Gene Expression Regulation chemistry ABCA1 biology.protein ATP-Binding Cassette Transporters |
| Zdroj: | Traffic. 8:1765-1777 |
| ISSN: | 1600-0854 1398-9219 |
| Popis: | Surfactant, highly enriched with phosphatidylcholine (PC), is secreted into the airspace by a classic apical secretory route, thereby maintaining lung stability. Herein, we show that adenoviral infection decreases surfactant PC in lungs by inhibiting its apical secretion and redirecting its export in alveolar cells by a basolateral route. These effects were not observed with replication-deficient adenovirus (Ad), specifically lacking early region 1 (E1) gene products. Adenoviral stimulation of basolateral PC export from cells was not observed after pharmacologic inhibition of ATP-binding cassette proteins, after introduction of small interfering RNA to the lipid pump ATP-binding cassette transporter A1 (ABCA1) or in ABCA1-defective human Tangier disease fibroblasts. Adenovirus and its E1A gene product increased ABCA1 levels by transcriptionally activating the ABCA1 gene. Thus, Ad lowers surfactant, in part, by triggering ABCA1-directed basolateral PC export, thereby limiting the cellular pool of surfactant PC destined for apical secretion. The results support a novel pathway, whereby a viral pathogen disrupts surfactant trafficking. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|