AUTHOR=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 , Becker Tim ,  the ALLIANCE Study Group as part of the German Centre for Lung Research (DZL) , Abdo Mustafa , Alcazar Miguel , Bahmer Thomas , Berbig Mira , Biller Heike , Bovermann Xenia , Brinkmann Folke , Calveron Mifflin-Rae , Chari Jirmo Adan , DeLuca David S. , Diekmann Gesa , Dittrich Anna-Maria , Dopfer Christian , Ege Markus , Foth Svenja , Fuchs Oliver , Gaedcke Svenja , Gaede Karoline I. , Grychtol Ruth , Habener Anika , Hansen Gesine , Happle Christine , Herzmann Christian , Hose Alexander , Illi Sabina , Kirsten Anne-Marie , Kohistani-Greif Naschla , König Inke R. , Koningsbruggen-Rietschel Silke Van , Kopp Matthias V. , Kurz Johanna , Landgraf-Rauf Katja , Laubhahn Kristina , Liboschik Lena , Liebl Claudia , Liselotte Husstedt Berrit , Liu Bin , Maison Nicole , Malik Aydin , Marzi Carola , Meyer Meike , Mutius Erika Von , Nissen Gyde , Nitsche Catharina , Pedersen Frauke , Price Mareike , Rabe Klaus F. , Renz Harald , Ricklefs Isabell , Rietschel Ernst , Roesler Barbara , Schaub Bianca , Schauberger Christina , Schildberg Tom , Schmidt-Weber Carsten , Schwerk Nicolaus , Skevaki Chrysanthi , Steinmetz Alena , Sultansei Laila , Szewczyk Marlen , Thiele Dominik , Veith Vera , Voigt Gesche , Waschki Benjamin , Watz Henrik , Weber Stefanie , Weckmann Markus , Welchering Nils , Zeitlmann Esther , Zissler Ulrich 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1021317

DOI=10.3389/fphar.2022.1021317

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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 (LTB<sub>4</sub>), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype.</p><p><bold>Methods:</bold> NGs from asthmatic nd healthy children were stimulated with 10 nM LTB<sub>4</sub>/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.</p><p><bold>Results:</bold> A reduced chemotactic response towards LTB<sub>4</sub> 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.</p><p><bold>Conclusions:</bold> Neutrophil migration <italic>in vitro</italic> 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.</p>