학술논문
Mitochondrial N-formyl methionine peptides contribute to exaggerated neutrophil activation in patients with COVID-19.
Document Type
Academic Journal
Author
Kuley R; Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA.; Center for Life Sciences, Mahindra University, Hyderabad, India.; Duvvuri B; Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA.; Wallin JJ; Biomarker Sciences, Gilead Sciences Inc, Foster City, CA, USA.; Bui N; Biomarker Sciences, Gilead Sciences Inc, Foster City, CA, USA.; Adona MV; Biomarker Sciences, Gilead Sciences Inc, Foster City, CA, USA.; O'Connor NG; Department of Medicine, University of Washington, Seattle, WA, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.; Sahi SK; Department of Medicine, University of Washington, Seattle, WA, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.; Stanaway IB; Department of Medicine, University of Washington, Seattle, WA, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.; Wurfel MM; Department of Medicine, University of Washington, Seattle, WA, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.; Morrell ED; Department of Medicine, University of Washington, Seattle, WA, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.; Liles WC; Department of Medicine, University of Washington, Seattle, WA, USA.; Sepsis Center of Research Excellence-UW (SCORE-UW), University of Washington, Seattle, WA, USA.; Bhatraju PK; Department of Medicine, University of Washington, Seattle, WA, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.; Sepsis Center of Research Excellence-UW (SCORE-UW), University of Washington, Seattle, WA, USA.; Lood C; Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA.
Source
Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE
Subject
Language
English
Abstract
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.