Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?-Reference-Cited by-同舟云学术

Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?

Published:2023-08-31 Issue:17 Volume:24 Page:13533
ISSN:1422-0067
Container-title:International Journal of Molecular Sciences
language:en
Short-container-title:IJMS

Author:

D’Amato Maura¹^ORCID,Campagnoli Monica¹,Iadarola Paolo²^ORCID,Bignami Paola Margherita²,Fumagalli Marco²,Chiarelli Laurent Roberto²^ORCID,Stelitano Giovanni²^ORCID,Meloni Federica³⁴,Linciano Pasquale⁵^ORCID,Collina Simona⁵^ORCID,Pietrocola Giampiero¹^ORCID,Vertui Valentina³^ORCID,Aliberti Anna⁶,Fossali Tommaso⁷,Viglio Simona¹^ORCID

Affiliation:

1. Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy

2. Department of Biology and Biotechnologies “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy

3. Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy

4. Transplant Unit, IRCCS Policlinico San Matteo, 27100 Pavia, Italy

5. Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy

6. Division of Anesthesiology and Intensive Care 1, IRCCS Policlinico San Matteo, 27100 Pavia, Italy

7. Department of Anesthesiology and Intensive Care, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, 20157 Milan, Italy

Abstract

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.

Funder

MUR Dipartimenti di Eccellenza

Fondazione Cariplo

Ministry of Health

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Link

https://www.mdpi.com/1422-0067/24/17/13533/pdf

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