1. In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma
- Author
-
Solveig Lemmel, Markus Weckmann, Anna Wohlers, Adan Chari Jirmo, Ruth Grychtol, Isabell Ricklefs, Gyde Nissen, Anna Bachmann, Shantanu Singh, Juan Caicedo, Thomas Bahmer, Gesine Hansen, Erika Von Mutius, Klaus F. Rabe, Oliver Fuchs, Anna-Maria Dittrich, Bianca Schaub, Christine Happle, Anne E. Carpenter, Matthias Volkmar Kopp, Tim Becker, the ALLIANCE Study Group as part of the German Centre for Lung Research (DZL), Mustafa Abdo, Miguel Alcazar, Mira Berbig, Heike Biller, Xenia Bovermann, Folke Brinkmann, Mifflin-Rae Calveron, David S. DeLuca, Gesa Diekmann, Christian Dopfer, Markus Ege, Svenja Foth, Svenja Gaedcke, Karoline I. Gaede, Anika Habener, Christian Herzmann, Alexander Hose, Sabina Illi, Anne-Marie Kirsten, Naschla Kohistani-Greif, Inke R. König, Silke Van Koningsbruggen-Rietschel, Matthias V. Kopp, Johanna Kurz, Katja Landgraf-Rauf, Kristina Laubhahn, Lena Liboschik, Claudia Liebl, Berrit Liselotte Husstedt, Bin Liu, Nicole Maison, Aydin Malik, Carola Marzi, Meike Meyer, Catharina Nitsche, Frauke Pedersen, Mareike Price, Harald Renz, Ernst Rietschel, Barbara Roesler, Christina Schauberger, Tom Schildberg, Carsten Schmidt-Weber, Nicolaus Schwerk, Chrysanthi Skevaki, Alena Steinmetz, Laila Sultansei, Marlen Szewczyk, Dominik Thiele, Vera Veith, Gesche Voigt, Benjamin Waschki, Henrik Watz, Stefanie Weber, Nils Welchering, Esther Zeitlmann, and Ulrich Zissler
- Subjects
neutrophil granulocytes ,migration ,LTB4 ,fMLP ,high-content image analysis ,single-cell analysis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
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.
- Published
- 2022
- Full Text
- View/download PDF