ATP/P2X7r axis mediates the pathological process of allergic asthma by inducing M2 polarization of alveolar macrophages. 2020

Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China.

Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1β and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization.

UI MeSH Term Description Entries
D008262 Macrophage Activation The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. Activation, Macrophage,Activations, Macrophage,Macrophage Activations
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016676 Macrophages, Alveolar Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells. Alveolar Macrophages,Macrophages, Pulmonary,Pulmonary Macrophages,Macrophage, Pulmonary,Pulmonary Macrophage,Alveolar Macrophage,Macrophage, Alveolar
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
April 2015, Inflammation,
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
January 2023, BMC pulmonary medicine,
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
May 2024, Inflammation research : official journal of the European Histamine Research Society ... [et al.],
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
August 2021, Journal of translational medicine,
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
January 2023, Allergologia et immunopathologia,
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
December 2017, Nature immunology,
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
March 2021, Allergy, asthma & immunology research,
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
January 2022, Frontiers in oncology,
Ruiting Li, and You Shang, and Xuemei Hu, and Yuan Yu, and Ting Zhou, and Wei Xiong, and Xiaojing Zou
January 2024, Naunyn-Schmiedeberg's archives of pharmacology,
Copied contents to your clipboard!