Lemmel, Solveig; Weckmann, Markus; Wohlers, Anna; Jirmo, Adan Chari; Grychtol, Ruth; Ricklefs, Isabell; Nissen, Gyde; Bachmann, Anna; Singh, Shantanu; Caicedo, Juan; Bahmer, Thomas; Hansen, Gesine; Von Mutius, Erika; Rabe, Klaus F; Fuchs, Oliver; Dittrich, Anna-Maria; Schaub, Bianca; Happle, Christine; Carpenter, Anne E; Kopp, Matthias Volkmar; ... (2022). In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma. Frontiers in Pharmacology, 13(1021317), p. 1021317. Frontiers 10.3389/fphar.2022.1021317
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Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype. Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort. Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration. Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine |
UniBE Contributor: |
Kopp, Matthias Volkmar |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1663-9812 |
Publisher: |
Frontiers |
Language: |
English |
Submitter: |
Anette van Dorland |
Date Deposited: |
31 Oct 2022 12:35 |
Last Modified: |
05 Dec 2022 16:27 |
Publisher DOI: |
10.3389/fphar.2022.1021317 |
PubMed ID: |
36304163 |
Uncontrolled Keywords: |
LTB4 fMLP high-content image analysis migration neutrophil granulocytes single-cell analysis |
BORIS DOI: |
10.48350/174252 |
URI: |
https://boris.unibe.ch/id/eprint/174252 |
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