title: Neutral lipid trafficking regulates alveolar type II cell surfactant phospholipid and surfactant protein expression.
abstract: Adipocyte differentiation-related protein (ADRP) is a critically important protein that mediates lipid uptake, and is highly expressed in lung lipofibroblasts (LIFs). Triacylglycerol secreted from the pulmonary circulation and stored in lipid storage droplets is a robust hormonal-, growth factor-, and stretch-regulated precursor for surfactant phospholipid synthesis by alveolar type II epithelial (ATII) cells. A549 lung epithelial cells rapidly take up green fluorescent protein (GFP)-ADRP fusion protein-associated lipid droplets (LDs) in a dose-dependent manner. The LDs initially localize to the perinuclear region of the cell, followed by localization in the cytoplasm. Uptake of ADRP-LDs causes a time- and dose-dependent increase in surfactant protein-B (SP-B) expression. This mechanism can be inhibited by either actinomycin D or cycloheximide, indicating that ADRP-LDs induce newly synthesized SP-B. ADRP-LDs concomitantly stimulate saturated phosphatidylcholine (satPC) synthesis by A549 cells, which is inhibited by ADRP antibody, indicating that this is a receptor-mediated mechanism. Intravenous administration of GFP-ADRP LDs to adult rats results in dose-dependent increases in lung ADRP and SP-B expression. These data indicate that lipofibroblast-derived ADRP coordinates ATII cells' synthesis of the surfactant phospholipid-protein complex by stimulating both satPC and SP-B. The authors propose, therefore, that ADRP is the physiologic determinant for the elusive coordinated, stoichiometric synthesis of surfactant phospholipid and protein by pulmonary ATII cells.
authors: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502-2006, USA. jtorday@labiomed.org
authors: John
authors: J
authors: Torday
authors: Virender
authors: V
authors: Rehan
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D000070780:Perilipin-2; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis* / Q000378:metabolism; D021381:Protein Transport; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008565:Membrane Proteins; D000070780:Perilipin-2; D010713:Phosphatidylcholines; D010743:Phospholipids; C000602984:Plin2 protein, rat; D037701:Pulmonary Surfactant-Associated Protein B