Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?
COVID-19
SARS-CoV-2
broncho-alveolar lavage (BAL)
human neutrophil elastase (HNE)
liquid chromatography–mass spectrometry (LC–MS)
lung
neutrophils
oxidation
reactive oxygen species (ROS)
α1-antitrypsin (AAT)
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
31 Aug 2023
31 Aug 2023
Historique:
received:
17
08
2023
revised:
28
08
2023
accepted:
30
08
2023
medline:
11
9
2023
pubmed:
9
9
2023
entrez:
9
9
2023
Statut:
epublish
Résumé
Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.
Identifiants
pubmed: 37686340
pii: ijms241713533
doi: 10.3390/ijms241713533
pmc: PMC10488172
pii:
doi:
Substances chimiques
Leukocyte Elastase
EC 3.4.21.37
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : MUR Dipartimenti di eccellenza
ID : F11I18000860001
Organisme : Ministry of Health funds to IRCCS Foundation Policlinico San Matteo Grant
ID : VISION 08069621
Organisme : Fondazione Cariplo
ID : COVIM project
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