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

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De Luca, Daniele and Shankar-Aguilera, Shivani and Autilio, Chiara and Raschetti, Roberto and Vedovelli, Luca and Fitting, Catherine and Payré, Christine and Jeammet, Louise and Pérez-Gil, Jesús and Cogo, Paola E. and Carnielli, Virgilio P. and Lambeau, Gérard and Touqui, Lhoussaine (2020) Surfactant-secreted phospholipase A2 interplay and respiratory outcome in preterm neonates. American Journal of Physiology - Lung Cellular and Molecular Physiology, 319 (1). L95-L104. ISSN 1040-0605; ESSN 1522-1504

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Official URL: https://doi.org/10.1152/ajplung.00462.2019



Abstract

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 ( 0.6; P 0.008; adjusted P 0.009), total phospholipids ( 0.475; P 0.05), and phosphatidylcholine ( 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 ( 0.679, P 0.005; adjusted P 0.04) and respiratory morbidity score at 12 mo postnatal age ( -b 0.349, P 0.037; adjusted P 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.


Item Type:Article
Uncontrolled Keywords:Lung injury; Newborn infant; Phospholipase A2; Prematurity; RDS; Surfactant
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Pneumology
ID Code:62316
Deposited On:28 Sep 2020 11:38
Last Modified:31 May 2021 10:26

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