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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Frei, RB; Luschnig, P; Parzmair, GP; Peinhaupt, M; Schranz, S; Fauland, A; Wheelock, CE; Heinemann, A; Sturm, EM.
Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen-induced pulmonary inflammation in mice.
Allergy. 2016; 71(7):944-956
Doi: 10.1111/all.12858
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Böhm Eva
- Frei-Winterleitner Robert
- Co-Autor*innen der Med Uni Graz
- Heinemann Akos
- Luschnig Petra
- Parzmair Gerald Peter
- Peinhaupt Miriam
- Schranz Silke
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- Abstract:
- Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o -dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2-AG into eicosanoids. Here, we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo. In vitro studies including CB2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow-derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA-induced asthma and directed eosinophil migration. CB2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB2 receptor agonist JWH-133 induced a moderate migratory response in eosinophils. However, short-term exposure to JWH-133 potently enhanced chemoattractant-induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB2 knockout mice and by using the selective CB2 antagonist SR144528. Of note, systemic application of JWH-133 clearly primed eosinophil-directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB2 -specific manner. This effect was completely absent in eosinophil-deficient ∆dblGATA mice. Our data indicate that CB2 may directly contribute to the pathogenesis of eosinophil-driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB2 -mediated priming of eosinophils. Hence, antagonism of CB2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
- Find related publications in this database (using NLM MeSH Indexing)
- Allergens - immunology
- Animals -
- Biomarkers -
- Calcium - metabolism
- Cannabinoids - pharmacology
- Cell Degranulation - immunology
- Cell Movement - drug effects
- Disease Models, Animal -
- Eosinophils - drug effects
- Eosinophils - immunology
- Eosinophils - metabolism
- Female -
- Gene Expression -
- Humans -
- Hypersensitivity - genetics
- Hypersensitivity - immunology
- Hypersensitivity - metabolism
- MAP Kinase Signaling System - drug effects
- Mice -
- Pertussis Toxin - immunology
- Pneumonia - etiology
- Pneumonia - metabolism
- Pneumonia - pathology
- Receptor, Cannabinoid, CB2 - agonists
- Receptor, Cannabinoid, CB2 - genetics
- Receptor, Cannabinoid, CB2 - metabolism
- rho-Associated Kinases - metabolism
- Find related publications in this database (Keywords)
- airway hyperresponsiveness
- Cannabinoid receptor 2
- Eosinophils
- Ovalbumin-induced asthma
- Priming