RT Journal Article
SR Electronic
T1 Balance between α-1Antitrypsin and Human Neutrophil Elastase (a1AT/HNE) in Bronchoalveolar Lavage fluid (BALf) of severe COVID19 patients
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2735
DO 10.1183/13993003.congress-2022.2735
VO 60
IS suppl 66
A1 V Vertui
A1 M D'Amato
A1 S Viglio
A1 S Bozzini
A1 M Morosini
A1 L Pandolfi
A1 S Lettieri
A1 M Della Zoppa
A1 T Fossali
A1 R Colombo
A1 A Aliberti
A1 P Iadarola
A1 F Meloni
YR 2022
UL http://erj.ersjournals.com/content/60/suppl_66/2735.abstract
AB Neutrophils (Neu) play a pathogenic role in COVID19 by releasing Neutrophils Extracellular Traps (NETs) or HNE. Being HNE inhibited by a1AT, supplementation of this protein has been proposed.We aim to study a1AT/HNE balance in BALf from ICU admitted COVID19 patients. To assess HNE, a1AT and HNE/a1AT complexes, 33 COVID 19 BALf samples were analysed by means of ELISA or gel-Electrophoresis + Western Blot. Proteins bound to a1AT or HNE were identified by Liquid chromatography-mass spectrometry. NETs release (PMA stimulated Neu +/− a1AT) was analysed by confocal microscopy. Both HNE and a1AT were clearly detectable in BALf at high levels. Contrary to what previously observed in other settings (Bronchiolits obliterans) (Cagnone, M. et al. High Throughput 2019; 8(1):5) we couldn’t detect any HNE/ a1AT complex in COVID19 even when purified HNE was added to samples (Fig 1a). HNE was found to be bound to acute phase proteins, histones and C3. Due to the relevant role of NETs, we assessed the ability of free a1AT to bind to histones. Although this binding was confirmed, a1AT wasn’t able to inhibit NETs formation (Fig 1b).Despite the finding of a high burden of free and bound HNE in COVID 19 BALf, the formation of HNE/ a1AT inhibitory complex is prevented. Furthermore, a1AT binds to histones but does not prevent NETs formation and their noxious activity.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 2735.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).