Neutrophil dysfunction in cystic fibrosis

•Microfluidic assays and advanced imaging technologies provide novel insight toward neutrophil function in individuals with cystic fibrosis (CF).•Neutrophils from individuals with CF display dysfunctional migration, cell-to-cell clustering, and phagocytosis.•Differences were noted between individual...

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Veröffentlicht in:Journal of cystic fibrosis 2021-11, Vol.20 (6), p.1062-1071
Hauptverfasser: Yonker, Lael M., Marand, Anika, Muldur, Sinan, Hopke, Alex, Leung, Hui Min, De La Flor, Denis, Park, Grace, Pinsky, Hanna, Guthrie, Lauren B., Tearney, Guillermo J., Irimia, Daniel, Hurley, Bryan P.
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Sprache:eng
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Zusammenfassung:•Microfluidic assays and advanced imaging technologies provide novel insight toward neutrophil function in individuals with cystic fibrosis (CF).•Neutrophils from individuals with CF display dysfunctional migration, cell-to-cell clustering, and phagocytosis.•Differences were noted between individuals with CF who were well and those experiencing a pulmonary exacerbation. Excessive neutrophil inflammation is the hallmark of cystic fibrosis (CF) airway disease. Novel technologies for characterizing neutrophil dysfunction may provide insight into the nature of these abnormalities, revealing a greater mechanistic understanding and new avenues for CF therapies that target these mechanisms. Blood was collected from individuals with CF in the outpatient clinic, CF individuals hospitalized for a pulmonary exacerbation, and non-CF controls. Using microfluidic assays and advanced imaging technologies, we characterized 1) spontaneous neutrophil migration using microfluidic motility mazes, 2) neutrophil migration to and phagocytosis of Staphylococcal aureus particles in a microfluidic arena, 3) neutrophil swarming on Candida albicans clusters, and 4) Pseudomonas aeruginosa-induced neutrophil transepithelial migration using micro-optical coherence technology (µOCT). Participants included 44 individuals: 16 Outpatient CF, 13 Hospitalized CF, and 15 Non-CF individuals. While no differences were seen with spontaneous migration, CF neutrophils migrated towards S. aureus particles more quickly than non-CF neutrophils (p 
ISSN:1569-1993
1873-5010
DOI:10.1016/j.jcf.2021.01.012