Elastase and myeloperoxidase participate in neutrophil extracellular trap release stimulated by SARS-CoV-2.

Authors

Juliana da Costa Silva, Cícero Almeida, Bruna M Souza Silva, Beatriz de S Bonfim, Ayda H Schneider, Anderson Dos Santos Ramos, Isadora Marques Paiva, Letícia S Galant, Ronaldo Martins, Daniel Macedo de Melo Jorge, Victor Ferreira Costa, Guilherme C Martelossi Cebinelli, Juliana E Toller-Kawahisa, Giovanni F Gomes, Gabriel Victor Lucena da Silva, Robertha M R Lemes, Gabriel Azevedo Publio, Fernanda M de Souza, Paulo Sérgio de A Augusto, Eurico Arruda, Paulo Louzada-Junior, Pérsio da Costa Roxo-Júnior, Larissa Cunha, Letícia Bonjorno, Renê de Oliveira, Ana Paula Carlotti, Thiago Mattar Cunha, José Carlos Alves-Filho, Fernando Queiroz Cunha

Published in

Journal of immunology (Baltimore, Md. : 1950). Volume 215. Issue 8. Aug 04, 2026.

Abstract

COVID-19 is a disease triggered by SARS-CoV-2 and some individuals develop a severe form that can progress to multiple organ failure. Neutrophils have been described as responsible for the release of neutrophil extracellular traps (NETs). The role of the elastase and myeloperoxidase (MPO) in NET release by neutrophils stimulated by SARS-CoV-2 infection was not addressed, and it was the aim of the present study. The NET release by human neutrophils infected with SARS-CoV-2 depends on elastase/MPO migration to the nucleus. Moreover, elastase/MPO migration is a consequence of PKC and PI3K kinase activation, leading to reactive oxygen species generation by the neutrophil mitochondria and NOX-2. We also reanalyzed the single-cell RNA sequencing data available in a database and demonstrated that neutrophils from bronchoalveolar lavage (BAL) fluid of patients with COVID-19 present increased expression of genes involved in the formation of the NOX2 complex, PKC delta and members of the PI3K family. In summary, the release of NETs by neutrophils in response to SARS-CoV-2 infection depends on the sequential activation of the PKC/PI3K/ROS pathway, inducing elastase/MPO migration to the nucleus triggering the NET formation. Thus, our study demonstrates new insights into the signaling pathways that induce NETs in response to SARS-CoV-2, highlighting new targets for studies and therapies for COVID-19.

PMID:
42555874
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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