Investigating the Link between Alpha-1 Antitrypsin and Human Neutrophil Elastase in Bronchoalveolar Lavage Fluid of COVID-19 Patients.
Curr Issues Mol Biol
; 44(5): 2122-2138, 2022 May 10.
Article
in English
| MEDLINE | ID: covidwho-1869490
ABSTRACT
Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to assess the content of HNE, α1-antitrypsin (AAT) and HNE-AAT complexes (the AAT/HNE balance) in 33 bronchoalveolar lavage fluid (BALf) samples from COVID-19 patients. These samples were submitted for Gel-Electrophoresis, Western Blot and ELISA, and proteins (bound to AAT or HNE) were identified by Liquid Chromatography-Mass Spectrometry. NETs' release was analyzed by confocal microscopy. Both HNE and AAT were clearly detectable in BALf at high levels. Contrary to what was previously observed in other settings, the formation of HNE-AAT complex was not detected in COVID-19. Rather, 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 AAT to bind to histones. While confirming this binding, AAT was not able to inhibit NET formation. In conclusion, despite the finding of a high burden of free and bound HNE, the lack of the HNE-AAT inhibitory complex in COVID-19 BALf demonstrates that AAT is not able to block HNE activity. Furthermore, while binding to histones, AAT does not prevent NET formation nor their noxious activity.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Language:
English
Journal:
Curr Issues Mol Biol
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
Cimb44050143
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