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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 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Frei-Winterleitner Robert
Heinemann Akos
Luschnig Petra
Parzmair Gerald Peter
Peinhaupt Miriam
Schranz Silke
Sturm Eva
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Number of Figures: 7
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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
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