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Surfactant-secreted phospholipase A2 interplay and respiratory outcome in preterm neonates.

Am J Physiol Lung Cell Mol Physiol. 2020 Jul 01;319(1):L95-L104. doi:10.1152/ajplung.00462.2019. Epub 2020 May 13
Daniele De Luca 1 , Shivani Shankar-Aguilera 1 , Chiara Autilio 2 , Roberto Raschetti 3 , Luca Vedovelli 4 , Catherine Fitting 5 , Christine Payré 6 , Louise Jeammet 6 , Jesus Perez-Gil 2 , Paola E Cogo 7 , Virgilio P Carnielli 8 , Gérard Lambeau 6 , Lhousseine Touqui 9
Daniele De Luca 1 , Shivani Shankar-Aguilera 1 , Chiara Autilio 2 , Roberto Raschetti 3 , Luca Vedovelli 4 , Catherine Fitting 5 , Christine Payré 6 , Louise Jeammet 6 , Jesus Perez-Gil 2 , Paola E Cogo 7 , Virgilio P Carnielli 8 , Gérard Lambeau 6 , Lhousseine Touqui 9
+ et al

[No authors listed]

Author information
  • 1 Cystic fibrosis and Bronchial diseases team-INSERM U938, Institut Pasteur, Paris, France.
  • 2 Department of Biochemistry and Molecular Biology, Faculty of Biology, and Research Institut-Hospital "12 de Octubre," Complutense University, Madrid, Spain.
  • 3 Division of Pediatrics and Neonatal Critical Care, "A.Béclère" Medical Center, South Paris University Hospitals, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
  • 4 PCare Laboratory, Fondazione Istituto di Ricerca Pediatrica "Città della Speranza," Padua, Italy.
  • 5 Cytokines and Inflammation Unit, Institut Pasteur, Paris, France.
  • 6 Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, Valbonne Sophia Antipolis, France.
  • 7 Division of Pediatrics, Department of Medicine and Surgery, University of Udine, Udine, Italy.
  • 8 Division of Neonatology, "G. Salesi" Women's and Children Hospital, Polytechnical University of Marche, Ancona, Italy.
  • 9 Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), Paris, France.

摘要


Secreted phospholipase A2 hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: 1) identify phospholipases A2 isoforms expressed in preterm lung; 2) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and 3) verify whether phospholipase A2 is linked to respiratory outcomes. In bronchoalveolar lavages of preterm neonates, we measured enzyme activity (alone or with inhibitors), enzyme subtypes, surfactant protein-A, and inflammatory mediators. Surfactant function and phospholipid profile were also tested. Urea ratio was used to obtain epithelial lining fluid concentrations. Follow-up data were prospectively collected. Subtype-IIA is the main phospholipase isoform in preterm lung, although subtype-IB may be significantly expressed. Neonates needing surfactant retreatment have higher enzyme activity (P = 0.021) and inflammatory mediators (P always ≤ 0.001) and lower amounts of phospholipids (P always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = -0.6; P = 0.008; adjusted P = 0.009), total phospholipids (ρ = -0.475; P = 0.05), and phosphatidylcholine (ρ = -0.622; P = 0.017). Exogenous surfactant significantly reduced global phospholipase activity (P < 0.001) and subtype-IIA (P = 0.005) and increased dioleoylphosphatidylglycerol (P < 0.001) and surfactant adsorption (P < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, P = 0.005; adjusted P = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ-b = 0.349, P = 0.037; adjusted P = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.

KEYWORDS: RDS, lung injury, newborn infant, phospholipase A2, prematurity, surfactant