In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma
oleh: Solveig Lemmel, Markus Weckmann, Markus Weckmann, Markus Weckmann, Anna Wohlers, Adan Chari Jirmo, Ruth Grychtol, Isabell Ricklefs, Isabell Ricklefs, Gyde Nissen, Gyde Nissen, Anna Bachmann, Shantanu Singh, Juan Caicedo, Thomas Bahmer, Thomas Bahmer, Gesine Hansen, Erika Von Mutius, Klaus F. Rabe, Oliver Fuchs, Oliver Fuchs, Oliver Fuchs, Anna-Maria Dittrich, Bianca Schaub, Christine Happle, Anne E. Carpenter, Matthias Volkmar Kopp, Matthias Volkmar Kopp, Matthias Volkmar Kopp, Tim Becker, Tim Becker, Tim Becker, the ALLIANCE Study Group as part of the German Centre for Lung Research (DZL), Mustafa Abdo, Miguel Alcazar, Thomas Bahmer, Mira Berbig, Heike Biller, Xenia Bovermann, Folke Brinkmann, Mifflin-Rae Calveron, Adan Chari Jirmo, David S. DeLuca, Gesa Diekmann, Anna-Maria Dittrich, Christian Dopfer, Markus Ege, Svenja Foth, Oliver Fuchs, Svenja Gaedcke, Karoline I. Gaede, Ruth Grychtol, Anika Habener, Gesine Hansen, Christine Happle, 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, Erika Von Mutius, Gyde Nissen, Catharina Nitsche, Frauke Pedersen, Mareike Price, Klaus F. Rabe, Harald Renz, Isabell Ricklefs, Ernst Rietschel, Barbara Roesler, Bianca Schaub, 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, Markus Weckmann, Nils Welchering, Esther Zeitlmann, Ulrich Zissler
| Format: | Article |
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| Diterbitkan: | Frontiers Media S.A. 2022-10-01 |
Deskripsi
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.