title: Thermodynamic and kinetic investigations of the release of oxidized phospholipids from lipid membranes and its effect on vascular integrity.
abstract: The lipid membrane not only provides a rich interface with an array of receptor signaling complexes with which a cell communicates, but it also serves as a source of lipid derived bioactive molecules. In pathologic conditions of acute lung injury (ALI) associated with activation of oxidative stress, unsaturated phosphatidyl cholines overlooking a luminal space undergo oxidation leading to generation of fragmented phospholipids such as 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (lysoPC), or 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) full length oxygenation products (oxPAPC). Using Langmuir monolayers as models of the lipid bilayer, we evaluated the propensity of these phospholipids to solubilize from the cell membrane. The results suggest that lysoPC is rapidly released as it is produced, while oxPAPC has a longer membrane bound lifetime. After being released from cell membranes, these oxidized phospholipids exhibit potent agonist-like effects on neighboring cells. Therefore, we correlate the presence of the two phospholipid groups with the onset and resolution of increased vascular leakiness associated with ALI through testing their effect on vascular endothelial barrier integrity. Our work shows that cells respond differently to these two groups of products of phosphatidyl choline oxidation. LysoPC disrupts cell-cell junctions and increases endothelial permeability while oxPAPC enhances endothelial barrier. These data suggest a model whereby rapid release of lysoPC results in onset of ALI associated vascular leak, and the release of a reserve of oxPAPC as oxidative stress subsides restores the vascular barrier properties.
authors.affiliation: Department of Chemistry, University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Charles T R
authors.initials: CT
authors.lastname: Heffern
authors.forename: Luka
authors.initials: L
authors.lastname: Pocivavsek
authors.forename: Anna A
authors.initials: AA
authors.lastname: Birukova
authors.forename: Nurgul
authors.initials: N
authors.lastname: Moldobaeva
authors.forename: Valery N
authors.initials: VN
authors.lastname: Bochkov
authors.forename: Ka Yee C
authors.initials: KY
authors.lastname: Lee
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Birukov
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D010084:Oxidation-Reduction; D010539:Permeability; D010713:Phosphatidylcholines / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D013816:Thermodynamics
chemical_list: C098435:2-arachidonoylglycero-3-phosphocholine; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; C472349:oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine; C006065:We 201
keywords: 1,2-dimyristoyl-sn-glycero-3-phosphocholine; 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-2n-glycero-3-phosphatidyl choline; 1-palmitoyl-2-arachnidoyl-sn-glycero-3-phosphocholine; 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine; ALI; CMC; Cell mechanics; DMPC; EC; Gibbs isotherm; Langmuir monolayer; Oxidized phospholipid; PAF-acetyl hydrolase; PAH; PAPC; PEIPC; Surface thermodynamics; TER; acute lung injury; critical micelle concentration; endothelial cells; full length PAPC oxygenation products; lysoPC; oxPAPC; transendothelial electrical resistance
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