GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma
Allergic asthma is a chronical pulmonary disease with high prevalence. It manifests as a maladaptive immune response to common airborne allergens and is characterized by airway hyperresponsiveness, eosinophilia, type 2 cytokine-associated inflammation, and mucus overproduction. Alveolar macrophages...
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doaj-3331845fc6a44070ad95d78d16710e522020-11-25T03:57:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-01217487748710.3390/ijms21207487GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic AsthmaKatharina M. Quell0Kuheli Dutta1Ülkü R. Korkmaz2Larissa Nogueira de Almeida3Tillman Vollbrandt4Peter König5Ian Lewkowich6George S. Deepe7Admar Vershoor8Jörg Köhl9Yves Laumonnier10Institute for Systemic Inflammation Research, University of Lübeck, 23538 Lübeck, GermanyInstitute for Systemic Inflammation Research, University of Lübeck, 23538 Lübeck, GermanyInstitute for Systemic Inflammation Research, University of Lübeck, 23538 Lübeck, GermanyInstitute for Systemic Inflammation Research, University of Lübeck, 23538 Lübeck, GermanyCell Analysis Core Facility, University of Lübeck, 23538 Lübeck, GermanyInstitute of Anatomy, University of Lübeck, 23538 Lübeck, GermanyDivision of Immunobiology, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USACollege of Medicine, University of Cincinnati, Cincinnati, OH 45229, USADepartment of Infectious Diseases and Microbiology, University of Lübeck, 23538 Lübeck, GermanyInstitute for Systemic Inflammation Research, University of Lübeck, 23538 Lübeck, GermanyInstitute for Systemic Inflammation Research, University of Lübeck, 23538 Lübeck, GermanyAllergic asthma is a chronical pulmonary disease with high prevalence. It manifests as a maladaptive immune response to common airborne allergens and is characterized by airway hyperresponsiveness, eosinophilia, type 2 cytokine-associated inflammation, and mucus overproduction. Alveolar macrophages (AMs), although contributing to lung homeostasis and tolerance to allergens at steady state, have attracted less attention compared to professional antigen-presenting and adaptive immune cells in their contributions. Using an acute model of house dust mite-driven allergic asthma in mice, we showed that a fraction of resident tissue-associated AMs, while polarizing to the alternatively activated M2 phenotype, exhibited signs of polynucleation and polyploidy. Mechanistically, in vitro assays showed that only Granulocyte-Macrophage Colony Stimulating Factor and interleukins IL-13 and IL-33, but not IL-4 or IL-5, participate in the establishment of this phenotype, which resulted from division defects and not cell-cell fusion as shown by microscopy. Intriguingly, mRNA analysis of AMs isolated from allergic asthmatic lungs failed to show changes in the expression of genes involved in DNA damage control except for <i>MafB</i>. Altogether, our data support the idea that upon allergic inflammation, AMs undergo DNA damage-induced stresses, which may provide new unconventional therapeutical approaches to treat allergic asthma.https://www.mdpi.com/1422-0067/21/20/7487allergic asthmaalveolar macrophagesdivision defectpolynucleationmouse model |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Katharina M. Quell Kuheli Dutta Ülkü R. Korkmaz Larissa Nogueira de Almeida Tillman Vollbrandt Peter König Ian Lewkowich George S. Deepe Admar Vershoor Jörg Köhl Yves Laumonnier |
spellingShingle |
Katharina M. Quell Kuheli Dutta Ülkü R. Korkmaz Larissa Nogueira de Almeida Tillman Vollbrandt Peter König Ian Lewkowich George S. Deepe Admar Vershoor Jörg Köhl Yves Laumonnier GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma International Journal of Molecular Sciences allergic asthma alveolar macrophages division defect polynucleation mouse model |
author_facet |
Katharina M. Quell Kuheli Dutta Ülkü R. Korkmaz Larissa Nogueira de Almeida Tillman Vollbrandt Peter König Ian Lewkowich George S. Deepe Admar Vershoor Jörg Köhl Yves Laumonnier |
author_sort |
Katharina M. Quell |
title |
GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma |
title_short |
GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma |
title_full |
GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma |
title_fullStr |
GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma |
title_full_unstemmed |
GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma |
title_sort |
gm-csf and il-33 orchestrate polynucleation and polyploidy of resident murine alveolar macrophages in a murine model of allergic asthma |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-10-01 |
description |
Allergic asthma is a chronical pulmonary disease with high prevalence. It manifests as a maladaptive immune response to common airborne allergens and is characterized by airway hyperresponsiveness, eosinophilia, type 2 cytokine-associated inflammation, and mucus overproduction. Alveolar macrophages (AMs), although contributing to lung homeostasis and tolerance to allergens at steady state, have attracted less attention compared to professional antigen-presenting and adaptive immune cells in their contributions. Using an acute model of house dust mite-driven allergic asthma in mice, we showed that a fraction of resident tissue-associated AMs, while polarizing to the alternatively activated M2 phenotype, exhibited signs of polynucleation and polyploidy. Mechanistically, in vitro assays showed that only Granulocyte-Macrophage Colony Stimulating Factor and interleukins IL-13 and IL-33, but not IL-4 or IL-5, participate in the establishment of this phenotype, which resulted from division defects and not cell-cell fusion as shown by microscopy. Intriguingly, mRNA analysis of AMs isolated from allergic asthmatic lungs failed to show changes in the expression of genes involved in DNA damage control except for <i>MafB</i>. Altogether, our data support the idea that upon allergic inflammation, AMs undergo DNA damage-induced stresses, which may provide new unconventional therapeutical approaches to treat allergic asthma. |
topic |
allergic asthma alveolar macrophages division defect polynucleation mouse model |
url |
https://www.mdpi.com/1422-0067/21/20/7487 |
work_keys_str_mv |
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