| First Author | Wong BH | Year | 2022 |
| Journal | J Biol Chem | Volume | 298 |
| Issue | 3 | Pages | 101709 |
| PubMed ID | 35150739 | Mgi Jnum | J:333161 |
| Mgi Id | MGI:7257369 | Doi | 10.1016/j.jbc.2022.101709 |
| Citation | Wong BH, et al. (2022) The lipid transporter Mfsd2a maintains pulmonary surfactant homeostasis. J Biol Chem :101709 |
| abstractText | Pulmonary surfactant is a lipoprotein complex essential for lung function, and insufficiency or altered surfactant composition is associated with major lung diseases such as acute respiratory distress syndromes, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Pulmonary surfactant is primarily composed of phosphatidylcholine (PC) in complex with specialized surfactant proteins and secreted by Alveolar Type 2 cells (AT2). Surfactant homeostasis on the alveolar surface is balanced by the rates of synthesis and secretion with re-uptake and recycling by AT2 cells, with some degradation by pulmonary macrophages and loss up the bronchial tree. However, whether phospholipid transporters exist in AT2 cells to mediate re-uptake of surfactant phospholipid remains to be identified. Here, we demonstrate that Major Facilitator Superfamily Domain containing 2a (Mfsd2a), a sodium-dependent lysophosphatidylcholine (LPC) transporter, is expressed at the apical surface of AT2 cells. A mouse model with inducible AT2 cell-specific deficiency of Mfsd2a exhibited AT2 cell hypertrophy with reduced total surfactant phospholipid levels due to reductions in the most abundant surfactants, phosphatidylcholine containing di-palmitic acid and phosphatidylcholine species containing the omega-3 fatty acid docosahexaenoic acid. These changes in surfactant levels and composition were mirrored by similar changes in the AT2 cell lipidome. Mechanistically, direct tracheal instillation of fluorescent LPC and PC probes indicated that Mfsd2a mediates the uptake of LPC generated by pulmonary phospholipase activity in the alveolar space. These studies reveal that Mfsd2a-mediated LPC uptake is quantitatively important in maintaining surfactant homeostasis and identify this lipid transporter as a physiological component of surfactant recycling. |
