학술논문
In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma
Document Type
article
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; Ulrich Zissler
Source
Frontiers in Pharmacology, Vol 13 (2022)
Subject
Language
English
ISSN
1663-9812
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.