title: Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells.
abstract: Maturation of fetal alveolar type II epithelial cells in utero is characterized by specific changes to lung surfactant phospholipids. Here, we quantified the effects of hormonal differentiation in vitro on the molecular specificity of cellular and secreted phospholipids from human fetal type II epithelial cells using electrospray ionization mass spectrometry. Differentiation, assessed by morphology and changes in gene expression, was accompanied by restricted and specific modifications to cell phospholipids, principally enrichments of shorter chain species of phosphatidylcholine (PC) and phosphatidylinositol, that were not observed in fetal lung fibroblasts. Treatment of differentiated epithelial cells with secretagogues stimulated the secretion of functional surfactant-containing surfactant proteins B and C (SP-B and SP-C). Secreted material was further enriched in this same set of phospholipid species but was characterized by increased contents of short-chain monounsaturated and disaturated species other than dipalmitoyl PC (PC16:0/16:0), principally palmitoylmyristoyl PC (PC16:0/14:0) and palmitoylpalmitoleoyl PC (PC16:0/16:1). Mixtures of these PC molecular species, phosphatidylglycerol, and SP-B and SP-C were functionally active and rapidly generated low surface tension on compression in a pulsating bubble surfactometer. These results suggest that hormonally differentiated human fetal type II cells do not select the molecular composition of surfactant phospholipid on the basis of saturation but, more likely, on the basis of acyl chain length.
authors.affiliation: Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton, UK. adp@soton.ac.uk
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Postle
authors.forename: Linda W
authors.initials: LW
authors.lastname: Gonzales
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bernhard
authors.forename: Graeme T
authors.initials: GT
authors.lastname: Clark
authors.forename: Marye H
authors.initials: MH
authors.lastname: Godinez
authors.forename: Rodolfo I
authors.initials: RI
authors.lastname: Godinez
authors.forename: Philip L
authors.initials: PL
authors.lastname: Ballard
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000737:chemistry; D013500:Surface Tension
chemical_list: D010713:Phosphatidylcholines; D010743:Phospholipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015060:1,2-Dipalmitoylphosphatidylcholine; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine; D004134:Dimyristoylphosphatidylcholine