Surfactant-secreted phospholipase A2interplay and respiratory outcome in preterm neonates

Author:

De Luca Daniele123ORCID,Shankar-Aguilera Shivani13,Autilio Chiara4,Raschetti Roberto1,Vedovelli Luca5,Fitting Catherine6,Payré Christine7,Jeammet Louise7,Perez-Gil Jesus4,Cogo Paola E.58,Carnielli Virgilio P.59,Lambeau Gérard7,Touqui Lhousseine310

Affiliation:

1. Division of Pediatrics and Neonatal Critical Care, “A.Béclère” Medical Center, South Paris University Hospitals, Assistance Publique – Hôpitaux de Paris (APHP), Paris, France

2. Physiopathology and Therapeutic Innovation Unit-INSERM U999, South Paris-Saclay University, Paris, France

3. Cystic fibrosis and Bronchial diseases team-INSERM U938, Institut Pasteur, Paris, France

4. Department of Biochemistry and Molecular Biology, Faculty of Biology, and Research Institut-Hospital “12 de Octubre,” Complutense University, Madrid, Spain

5. PCare Laboratory, Fondazione Istituto di Ricerca Pediatrica “Città della Speranza,” Padua, Italy

6. Cytokines and Inflammation Unit, Institut Pasteur, Paris, France

7. Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, Valbonne Sophia Antipolis, France

8. Division of Pediatrics, Department of Medicine and Surgery, University of Udine, Udine, Italy

9. Division of Neonatology, “G. Salesi” Women’s and Children Hospital, Polytechnical University of Marche, Ancona, Italy

10. Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), Paris, France

Abstract

Secreted phospholipase A2hydrolyzes 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 A2isoforms 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 A2is 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.

Funder

ADRN

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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