title: 18:1/18:1-Dioleoyl-phosphatidylglycerol prevents alveolar epithelial apoptosis and profibrotic stimulus in a neonatal piglet model of acute respiratory distress syndrome.
abstract: BACKGROUND
  18:1/18:1-Dioleoyl-phosphatidylgycerol (DOPG) is a surfactant phospholipid that is nearly non-detectable in neonatal surfactant films. When alveolar macrophages are exposed to DOPG in vitro, secretory phospholipase A2 (sPLA2) production is blocked, resulting in suppressed macrophage activity and improved surfactant function. We investigated whether the addition of DOPG to a commercially available surfactant preparation would improve lung function in a neonatal piglet model of acute respiratory distress syndrome.
  
  
  METHODS
  Respiratory failure was achieved by triple-hit lung injury (repeated broncho-alveolar lavage, injurious ventilation, tracheal lipopolysaccharide instillation, each intervention 24 h apart) in twenty-four domestic piglets aged 2-6 days and subject to mechanical ventilation. Following each lung injury protocol the piglets were treated with surfactant alone or with surfactant + DOPG.
  
  
  RESULTS
  Within 72 h of mechanical ventilation, we observed significantly improved gas exchange (oxygenation and ventilation), lung mechanics (compliance and resistance of the respiratory system), and pulmonary oedema (extra-vascular lung water index) in the surfactant + DOPG group. This favourable clinical effect could be attributed to improved surfactant function, reduced sPLA2 secretion, inhibition of macrophage migration, reduced alveolar epithelial apoptosis, and suppression of amphiregulin and TGF-β1 expression in pulmonary tissues as a prerequisite for fibrous lung repair.
  
  
  CONCLUSIONS
  We conclude that surfactant fortified by DOPG preserves lung function, and prevents alveolar epithelial injury and fibrous stimulus by reduction of sPLA2 in a neonatal model of acute respiratory distress syndrome without any relevant discernable side effects. Hence, DOPG supplementation in a neonatal lung exerts important function protecting effects and seems to be justified in cases of overwhelming pulmonary inflammation.
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Preuß
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Scheiermann
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Stadelmann
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany.
authors.forename: Friede D
authors.initials: FD
authors.lastname: Omam
authors.affiliation: Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Supandi
authors.initials: S
authors.lastname: Winoto-Morbach
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Lex
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: von Bismarck
authors.affiliation: Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Adam-Klages
authors.affiliation: Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Knerlich-Lukoschus
authors.affiliation: Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Wesch
authors.affiliation: Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Janka
authors.initials: J
authors.lastname: Held-Feindt
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.affiliation: Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schütze
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany. Electronic address: m.krause@pediatrics.uni-kiel.de.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Krause
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D011654:Pulmonary Edema / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000517:prevention & control; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000517:prevention & control*; D013552:Swine
chemical_list: D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol
keywords: (Neonatal) acute respiratory distress syndrome; Airway epithelial cells; Epithelial-to-mesenchymal transition; Fibrous lung repair; Phosphatidylglycerols; Secretory phospholipase A2