GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma.

Abstract

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 MafB. 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.

• Authors: Katharina M Quell, Kuheli Dutta, Ülkü R Korkmaz, Larissa Nogueira de Almeida, Tillman Vollbrandt, Peter König, Ian Lewkowich, George S Deepe Jr, Admar Verschoor, Jörg Köhl, Yves Laumonnier
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 20 (10 11 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33050608 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Histocompatibility Antigens Class II
• IL33 protein, human
• Interleukin-33
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Asthma (etiology, metabolism, pathology)
• Biomarkers
• Disease Models, Animal
• Disease Susceptibility
• Fluorescent Antibody Technique
• Gene Expression
• Giant Cells (drug effects, metabolism)
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• Histocompatibility Antigens Class II (immunology)
• Interleukin-33 (pharmacology)
• Macrophage Activation
• Macrophages, Alveolar (cytology, drug effects, metabolism)
• Mice
• Polyploidy