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Targeting C5aR1 signaling reduced neutrophil extracellular traps and ameliorates COVID-19 pathology
Bruna M. Silva; Flavio Protasio Veras; Giovanni Gomes; Seppe Cambier; Gabriel Silva; Andreza Quadros; Diego Caetite; Daniele Nascimento; Camila Silva; Juliana Silva; Samara Damasceno; Ayda Schneider; Fabio Beretta; Sabrina Batah; Icaro Castro; Isadora Paiva; Tamara Rodrigues; Ana C G Salina; Ronaldo Martins; Guilherme Cebinelli; Naira Bibo; Daniel Jorge; Helder I Nakaya; Dario S Zamboni; Luiz Leiria; Alexandre Fabro; Jose C Alves-Filho; Eurico Arruda; Paulo Louzada-Junior; Rene Oliveira; Larissa D. Cunha; Pierre Van-Mol; Lore Vanderbeke; Simon Feys; Els Wauters; Laura Brandolini; Fernando Cunha; Jorg Kohl; Marcello Allegretti; Diether Lambrechts; Joost Wauters; Paul Proost; Thiago M Cunha.
Afiliación
  • Bruna M. Silva; University of Sao Paulo
  • Flavio Protasio Veras; University of Sao Paulo
  • Giovanni Gomes; University of Sao Paulo
  • Seppe Cambier; Ku Leuven
  • Gabriel Silva; University of Sao Paulo
  • Andreza Quadros; University of Sao Paulo
  • Diego Caetite; University of Sao Paulo
  • Daniele Nascimento; University of Sao Paulo
  • Camila Silva; University of Sao Paulo
  • Juliana Silva; University of Sao Paulo
  • Samara Damasceno; University of Sao Paulo
  • Ayda Schneider; University of Sao Paulo
  • Fabio Beretta; KU Leuven
  • Sabrina Batah; University of Sao Paulo
  • Icaro Castro; Hospital Israelita Albert Einstein
  • Isadora Paiva; University of Sao Paulo
  • Tamara Rodrigues; University of Sao Paulo
  • Ana C G Salina; University of Sao Paulo
  • Ronaldo Martins; University of Sao Paulo
  • Guilherme Cebinelli; University of Sao Paulo
  • Naira Bibo; University of Sao Paulo
  • Daniel Jorge; University of Sao Paulo
  • Helder I Nakaya; Hospital Israelita Albert Einstein
  • Dario S Zamboni; Universidade de Sao Paulo
  • Luiz Leiria; University of Sao Paulo
  • Alexandre Fabro; University of Sao Paulo
  • Jose C Alves-Filho; University of Sao Paulo
  • Eurico Arruda; University of Sao Paulo
  • Paulo Louzada-Junior; University of Sao Paulo
  • Rene Oliveira; University of Sao Paulo
  • Larissa D. Cunha; University of Sao Paulo
  • Pierre Van-Mol; KU Leuven
  • Lore Vanderbeke; KU Leuven
  • Simon Feys; KU Leuven
  • Els Wauters; KU Leuven
  • Laura Brandolini; Dompe
  • Fernando Cunha; University of Sao Paulo
  • Jorg Kohl; University of Lubeck
  • Marcello Allegretti; Dompe
  • Diether Lambrechts; KU Leuven
  • Joost Wauters; KU Leuven
  • Paul Proost; KU Leuven
  • Thiago M Cunha; University of Sao Paulo
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-498624
ABSTRACT
Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonist of C5aR1 could be useful for COVID-19 treatment.
Licencia
cc_by_nc_nd
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2022 Tipo del documento: Preprint