TY - JOUR T1 - Acutely lethal H1N1 influenza A virus infection alters the murine alveolar type II cell surfactant lipidome JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA2612 VL - 48 IS - suppl 60 SP - PA2612 AU - Ian Davis AU - Parker Woods AU - Lauren Doolittle Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA2612.abstract N2 - Alveolar type II (ATII) cells are a primary site of influenza A virus replication. We have shown that influenza infection significantly impairs murine ATII cell surfactant protein synthesis. However, the impact of infection on surfactant lipid metabolism has not been determined at the level of the ATII cell. We hypothesized that influenza infection results in significant dysregulation of ATII cell lipid metabolism which contributes to altered surfactant composition and impaired surfactant function in infected mice.Objective: To define effects of acutely lethal influenza A virus infection in vivo on the murine ATII cell surfactant lipidome.Methods: C57BL/6 mice were inoculated intranasally with 10,000 pfu/mouse influenza A/WSN/33 (H1N1) or mock-infected with virus diluent. ATII cells were isolated from euthanized mice (n=5-6/group) by a standard lung digestion protocol at 6 days post-inoculation (d.p.i.). UHPLC/MS was used to measure levels of 115 lipid-related compounds of known identity in methanol extracts from each ATII cell sample.Results: Relative to mock-infected controls, levels of more than 80% of analyzed ATII cell lipid metabolites significantly increased or decreased at 6 d.p.i. Major surfactant phospholipids (DPPC, DPPG, and phosphatidylethanolamine) significantly decreased but cholesterol and sphingosine content was higher at 6 d.p.i. Phospholipid precursors were reduced but degradatory phospholipid metabolites, palmitoylated lysophospholipids, long-chain fatty acids, and PUFAs increased.Conclusions: Altered ATII cell surfactant lipid metabolism may contribute significantly to development of reduced lung compliance and onset of ARDS in influenza-infected mice. ER -