Oxidative and Proteolytic Inactivation of Alpha-1 Antitrypsin in Bronchopulmonary Dysplasia Pathogenesis: A Top-Down Proteomic Bronchoalveolar Lavage Fluid Analysis

Frontiers in Pediatrics

Federica Iavarone¹  Simonetta Costa²  Claudia Aurilia²  Chiara Tirone²  Alessandra Lio²  Milena Tana²  Giovanni Vento³  Irene Messana⁴  Massimo Castagnola⁵ 

[1] Dipartimento di Scienze Biotecnologiche di base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy;Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy;Dipartimento di Scienze della Vita e Sanità Pubblica, Unità Operativa Complessa di Neonatologia, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy;Dipartimento di Scienze della Vita e Sanità Pubblica, Unità Operativa Complessa di Neonatologia, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy;Università Cattolica del Sacro Cuore, Istituto di Clinica Pediatrica, Rome, Italy;Istituto di Scienze e Tecnologie Chimiche “Giulio Natta,” Consiglio Nazionale delle Ricerche, Rome, Italy;Laboratorio di Proteomica e Metabonomica-Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, Rome, Italy;

关键词: alpha-1 antitrypsin;    preterm infants;    bronchopulmonary displasia;    bronchoalveolar lavage fluid;    proteomics;   

DOI  :  10.3389/fped.2021.597415

来源: Frontiers

【 摘 要 】

The study investigates the role of the oxidative and proteolytic inactivation of alpha-1 antitrypsin (AAT) in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature infants. Bronchoalveolar lavage fluid (BALF) samples were collected on the 3rd day of life from mechanically ventilated neonates with gestational age ≤ 30 weeks and analyzed without previous treatment (top-down proteomics) by reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. AAT fragments were identified by high-resolution LTQ Orbitrap XL experiments and the relative abundances determined by considering the extracted ion current (XIC) peak area. Forty preterm neonates were studied: 20 (50%) did not develop BPD (no-BPD group), 17 (42.5%) developed mild or moderate new-BPD (mild + moderate BPD group), and 3 (7.5%) developed severe new-BPD (severe BPD group). Eighteen fragments of AAT and a fragment of AAT oxidized at a methionine residue were identified: significantly higher values of AAT fragments 25–57, 375–418, 397–418, 144–171, and 397–418 with oxidized methionine were found in the severe BPD group. The significantly higher levels of several AAT fragments and of the fragment 397–418, oxidized in BALF of preterm infants developing BPD, underlie the central role of an imbalance between proteases and protease inhibitors in exacerbating lung injury and inducing most severe forms of BPD. The study has some limitations, and between them, the small sample size implies the need for further confirmation by larger studies.

【 授权许可】

CC BY