Mitochondrial N-formyl methionine peptides contribute to exaggerated neutrophil activation in patients with COVID-19

Neutrophil dysregulation is well established in COVID-19. However, factors contributing to neutrophil activation in COVID-19 are not clear. We assessed if N-formyl methionine (fMet) contributes to neutrophil activation in COVID-19. Elevated levels of calprotectin, neutrophil extracellular traps (NET...

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Main Authors: Runa Kuley, Bhargavi Duvvuri, Jeffrey J. Wallin, Nam Bui, Mary Vic Adona, Nicholas G. O’Connor, Sharon K. Sahi, Ian B. Stanaway, Mark M. Wurfel, Eric D. Morrell, W. Conrad Liles, Pavan K. Bhatraju, Christian Lood
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Virulence
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Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2023.2218077
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Summary:Neutrophil dysregulation is well established in COVID-19. However, factors contributing to neutrophil activation in COVID-19 are not clear. We assessed if N-formyl methionine (fMet) contributes to neutrophil activation in COVID-19. Elevated levels of calprotectin, neutrophil extracellular traps (NETs) and fMet were observed in COVID-19 patients (n = 68), particularly in critically ill patients, as compared to HC (n = 19, p < 0.0001). Of note, the levels of NETs were higher in ICU patients with COVID-19 than in ICU patients without COVID-19 (p < 0.05), suggesting a prominent contribution of NETs in COVID-19. Additionally, plasma from COVID-19 patients with mild and moderate/severe symptoms induced in vitro neutrophil activation through fMet/FPR1 (formyl peptide receptor-1) dependent mechanisms (p < 0.0001). fMet levels correlated with calprotectin levels validating fMet-mediated neutrophil activation in COVID-19 patients (r = 0.60, p = 0.0007). Our data indicate that fMet is an important factor contributing to neutrophil activation in COVID-19 disease and may represent a potential target for therapeutic intervention.
ISSN:2150-5594
2150-5608