期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 63, 期 3, 页码 327-337出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2019-0413OC
关键词
meconium aspiration syndrome; neonatal acute respiratory distress syndrome; pulmonary surfactant; lung aeration; surfactant proteins
资金
- European Society of Pediatric Research Young Investigator Start-up Award 2017
- Association pour la Recherche et le Developpement en Neonatologie [ADRN-2016/2018]
- Spanish Ministry of Science and Innovation [RTI2018-094564-BI00]
- Regional Government of Madrid [P2018/NMT-4389]
No in vivo data are available regarding the effect of meconium on human surfactant in the early stages of severe meconium aspiration syndrome (MAS). In the present study, we sought to characterize the changes in surfactant composition, function, and structure during the early phase of meconium injury. We designed a translational prospective cohort study of nonbronchoscopic BAL of neonates with severe MAS (n= 14) or no lung disease (n = 18). Surfactant lipids were analyzed by liquid chromatography-high-resolution mass spectrometry. Secretory phospholipase A(2) subtypes IB, V, and X and SP-A (surfactant protein A) were assayed by ELISA. SP-B and SP-C were analyzed by Western blotting under both nonreducing and reducing conditions. Surfactant function was assessed by adsorption test and captive bubble surfactometry, and lung aeration was evaluated by semiquantitative lung ultrasound. Surfactant nanostructure was studied using cryo-EM and atomic force microscopy. Several changes in phospholipid subclasses were detected during MAS. Lysophosphatidylcholine species released by phospholipase A(2) hydrolysis were increased. SP-B and SP-C were significantly increased together with some shorter immature forms of SP-B. Surfactant function was impaired and correlated with poor lung aeration. Surfactant nanostructure was significantly damaged in terms of vesicle size, tridimensional complexity, and compactness. Various alterations of surfactant phospholipids and proteins were detected in the early phase of severe meconium aspiration and were due to hydrolysis and inflammation and a defensive response. This impairs both surfactant structure and function, finally resulting in reduced lung aeration. These findings support the development of new surfactant protection and antiinflammatory strategies for severe MAS.
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