ATP/P2X7r axis mediates the pathological process of allergic asthma by inducing M2 polarization of alveolar macrophages

Li, Ruiting; Shang, You; Hu, Xuemei; Yuan, Yu; Zhou, Ting; Xiong, Wei; Zou, Xiaojing

doi:10.1016/j.yexcr.2019.111708

Cited by 27 publications

(20 citation statements)

References 48 publications

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“…AMs, which are the most important resident macrophages in the lung, act as immune barriers in the alveoli against several pathogens of the respiratory tract (61). Alveolar macrophages are highly heterogeneous and exhibit unique phenotypes and functions in the complex microenvironment of the body (62).…”

Section: M2 Macrophagesmentioning

confidence: 99%

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

Zhu

Lü

2021

Mol Med Rep

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Type 2 innate lymphoid cells (ILC2s) are important innate immune cells that are involved in type 2 inflammation, in both mice and humans. ILC2s are stimulated by factors, including interleukin (IL)-33 and IL-25, and activated ILC2s secrete several cytokines that mediate type 2 immunity by inducing profound changes in physiology, including activation of alternative (M2) macrophages. M2 macrophages possess immune modulatory, phagocytic, tissue repair and remodeling properties, and can regulate ILC2s under infection. The present review summarizes the role of ILC2s as innate cells and M2 macrophages as anti-inflammatory cells, and discusses current literature on their important biological significance. The present review also highlights how the crosstalk between ILC2s and M2 macrophages contributes to lung development, induces pulmonary parasitic expulsion, exacerbates pulmonary viral and fungal infections and allergic airway diseases, and promotes the development of lung diseases, such as pulmonary fibrosis, chronic obstructive pulmonary disease and carcinoma of the lungs. Contents

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Section: M2 Macrophagesmentioning

confidence: 99%

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

Zhu

Lü

2021

Mol Med Rep

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“…ATP is involved directly in airway inflammation (a key hallmark of asthma) through activation of a variety of immune cell types, including eosinophils (4,5), mast cells (6,7), dendritic cells (8)(9)(10), and alveolar macrophages (11)(12)(13). Furthermore, both ATP and adenosine (a breakdown product of ATP) have been shown to have pro-asthmatic roles within the epithelia by stimulating mucin production (14,15), and adenosine also upregulates fibronectin expression and therefore may be involved in airway remodeling (16).…”

Section: Introductionmentioning

confidence: 99%

Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?

et al. 2021

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Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.

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“…Interestingly, the presence of micronuclei has been shown to activate STING and cGAS pathways [ 46 ] and may be a cause for type I Interferon production by AMs [ 47 ], a phenomenon previously observed in activated AMs [ 48 , 49 ]. Congruent with a lack of involvement of cell fusion in vitro using PKH26 and CFSE-labeled cells, we did not observe changes in the expression of genes reported to be involved in such mechanisms in vivo, such as connexin 43, associated with syncytial trans-epithelial alveolar communication [ 50 ], or PanX1 and P2X7R, receptors contributing to the cell fusion mechanisms [ 21 , 51 ] and participating in allergic asthma pathology [ 52 ]. Intriguingly, although tAMs showed clear signs of DNA damage, we did not evidence changes in genes controlling the response to such insults, such as Trp53 , C-myc and Atr expression.…”

Section: Discussionmentioning

confidence: 99%

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

Quell

Dutta

Korkmaz

et al. 2020

IJMS

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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.

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ATP/P2X7r axis mediates the pathological process of allergic asthma by inducing M2 polarization of alveolar macrophages

Cited by 27 publications

References 48 publications

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?

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

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