PuSH - Publikationsserver des Helmholtz Zentrums München: <em>In vitro</em> neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma.

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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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