Frontiers in Pharmacology (Oct 2022)
In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma
- 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
Affiliations
- Solveig Lemmel
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Markus Weckmann
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Markus Weckmann
- Priority Research Area Chronic Lung Diseases Leibniz Lung Research Center Borstel, Epigenetics of Chronic Lung Disease, Großhansdorf, Germany
- Markus Weckmann
- Airway Research Center North, Member of the German Center of Lung Research (DZL), Lübeck, Germany
- Anna Wohlers
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Adan Chari Jirmo
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center of Lung Research (DZL), Hannover, Germany
- Ruth Grychtol
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center of Lung Research (DZL), Hannover, Germany
- Isabell Ricklefs
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Isabell Ricklefs
- Airway Research Center North, Member of the German Center of Lung Research (DZL), Lübeck, Germany
- Gyde Nissen
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Gyde Nissen
- Airway Research Center North, Member of the German Center of Lung Research (DZL), Lübeck, Germany
- Anna Bachmann
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Shantanu Singh
- Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, CA, United States
- Juan Caicedo
- Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, CA, United States
- Thomas Bahmer
- Department of Pneumology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
- Thomas Bahmer
- University Hospital Schleswig-Holstein Campus Kiel, Department for Internal Medicine I, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Kiel, Germany
- Gesine Hansen
- Airway Research Center North, Member of the German Center of Lung Research (DZL), Lübeck, Germany
- Erika Von Mutius
- University Children’s Hospital, Ludwig Maximilian’s University, German Research Center for Environmental Health (CPC-M), Member of the German Center of Lung Research (DZL), Munich, Germany
- Klaus F. Rabe
- Department of Pneumology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
- Oliver Fuchs
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Oliver Fuchs
- University Children’s Hospital, Ludwig Maximilian’s University, German Research Center for Environmental Health (CPC-M), Member of the German Center of Lung Research (DZL), Munich, Germany
- Oliver Fuchs
- Department of Paediatric Respiratory Medicine, Inselspital, University Children’s Hospital of Bern, University of Bern, Bern, Switzerland
- Anna-Maria Dittrich
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center of Lung Research (DZL), Hannover, Germany
- Bianca Schaub
- University Children’s Hospital, Ludwig Maximilian’s University, German Research Center for Environmental Health (CPC-M), Member of the German Center of Lung Research (DZL), Munich, Germany
- Christine Happle
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center of Lung Research (DZL), Hannover, Germany
- Anne E. Carpenter
- Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, CA, United States
- Matthias Volkmar Kopp
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Matthias Volkmar Kopp
- Airway Research Center North, Member of the German Center of Lung Research (DZL), Lübeck, Germany
- Matthias Volkmar Kopp
- Department of Paediatric Respiratory Medicine, Inselspital, University Children’s Hospital of Bern, University of Bern, Bern, Switzerland
- Tim Becker
- Department of Paediatric Pneumology and Allergology, University Children’s Hospital, Lübeck, Schleswig-Holstein, Germany
- Tim Becker
- Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, CA, United States
- Tim Becker
- 0IAV GmbH, Gifhorn, Germany
- 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
- DOI
- https://doi.org/10.3389/fphar.2022.1021317
- Journal volume & issue
-
Vol. 13
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.
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