Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Frei, R.
THE ROLE OF CB2 - RECEPTOR LIGANDS IN EOSINOPHIL FUNCTION
[ Diplomarbeit/Master Thesis ] Karl-Franzens-Universität Graz; 2011. pp.60.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Böhm Eva
- Groschner Klaus
- Heinemann Akos
- Altmetrics:
- Abstract:
- Eosinophils play a key role in allergic diseases such as bronchial asthma and atopic derma-titis. A prominent feature of these diseases is the accumulation of eosinophils in inflamed tissue induced by several chemoattractants. After discovery of the endocannabinoid system and investigation of several endogenous and synthetic ligands, evidence grew up that can-nabinoids, especially CB2-receptor ligands may play a major role in mediating inflammato-ry responses. It was shown that they possess the ability to induce and to inhibit migration of various immune cells including eosinophils. In the first part of this study we investigated the effects of several cannabinoids on human eosinophil shape change responses towards eotaxin or prostaglandin D2 (PGD2). We found that the endocannabinoid 2-arachidonoylglycerol (2-AG) as well as the synthetic cannabi-noid JWH-133 increase shape change responses induced by eotaxin, whereas the endocan-nabinoid anandamide (AEA) and O-1602 dont affect eosinophil shape change responses induced by PGD2. The effect of both 2-AG and JWH-133 could be decreased by the CB2-receptor antagonist/inverse agonist AM630, indicating the involvement of CB2-receptor activation. In the second part of the study we focused on eosinophil chemotaxis experiments, where we could show that JWH-133 significantly inhibited eosinophil migration towards PGD2. Treatment with the CB2-receptor antagonist SR144528 was able to partially decrease the JWH-133 mediated effect. O-1602 showed no markedly effect on eosinophil chemotaxis, whereas the endocannabinoid AEA significantly affected eosinophil responses. Treatment with AM630 abolished the AEA-mediated effects. Further we investigated the effects of cannabinoids on eosinophil apoptosis and observed a slight pro-apoptotic effect of the selective CB2-receptor agonist JWH-133. Taken together, CB receptor agonists modulate eosinophil function such as shape change and chemotaxis, but still it remains unclear whether they induce pro-or anti-inflammatory effects. Thus further studies to investigate the CB2 mediated effects in detail have to be conducted.