Elastase and myeloperoxidase participate in neutrophil extracellular trap release stimulated by SARS-CoV-2
Abstract
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.
Article Details
Journal Info
The Journal of Immunology
American Association of Immunologists
Authors (29)
Juliana da Costa Silva
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Cícero Almeida
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Bruna M Souza Silva
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Beatriz de S Bonfim
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Ayda H Schneider
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Anderson dos Santos Ramos
Center for Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo
Isadora Marques Paiva
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Letícia S Galant
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Ronaldo Martins
Daniel Macedo de Melo Jorge
Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Victor Ferreira Costa
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Guilherme C Martelossi Cebinelli
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Juliana E Toller-Kawahisa
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Giovanni F Gomes
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Gabriel Victor Lucena da Silva
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Robertha M R Lemes
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Gabriel Azevedo Publio
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Fernanda M de Souza
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Paulo Sérgio de A Augusto
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Eurico Arruda
Paulo Louzada-Junior
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Pérsio da Costa Roxo-Júnior
Division of Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Larissa Cunha
Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Letícia Bonjorno
Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Renê de Oliveira
Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Ana Paula Carlotti
Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto , São Paulo,
Thiago Mattar Cunha
Jose Carlos Alves-Filho
Fernando Queiroz Cunha
Center for Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo