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Lemmel, S.* ; Weckmann, M.* ; Wohlers, A.* ; Jirmo, A.C.* ; Grychtol, R.* ; Ricklefs, I.* ; Nissen, G.* ; Bachmann, A.* ; Singh, S.* ; Caicedo, J.C.* ; Bahmer, T.* ; Hansen, G.* ; ALLIANCE Study Group (von Mutius, E. ; Illi, S. ; Maison, N. ; Schmidt-Weber, C.B. ; Zissler, U.M.) ; Rabe, K.F.* ; Fuchs, O.* ; Dittrich, A.M.* ; Schaub, B.* ; Happle, C.* ; Carpenter, A.E.* ; Kopp, M.V.* ; Becker, T.*

In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma.

Front. Pharmacol. 13:1021317 (2022)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Fmlp ; High-content Image Analysis ; Ltb4 ; Migration ; Neutrophil Granulocytes ; Single-cell Analysis

ISSN (print) / ISBN 1663-9812

e-ISSN 1663-9812

Journal Frontiers in Pharmacology

Quellenangaben Volume: 13, Article Number: 1021317

Publisher Frontiers

Publishing Place Lausanne

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Asthma and Allergy Prevention (IAP)
Institute for Allergy Research (IAF)

Grants Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
National Institutes of Health
University of Luebeck
Immune Regulation of Inflammation in Allergy and Infection