Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schranz, S.
The role of GPR55 agonists in the function of human eosinophils.
[ Diplomarbeit/Master Thesis ] Karl-Franzens-University Graz; 2011. pp.59.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Böhm Eva
- Heinemann Akos
- Altmetrics:
- Abstract:
- Eosinophils are important effector cells in inflammatory and allergic processes and are currently considered as a major therapeutic target in allergic diseases and asthma. The eosinophil was discovered by Jones in 1846 but its proclivity to stain with aniline dyes was first described by Paul Ehrlich in 1879. Eosinophils are characterized by their abundant cytoplasm with coarse reflective granules and a bi-lobed nucleus. Several lipid mediators such as prostaglandins, thromboxanes as well as endocannabinoids are fundamentally involved in the pathogenesis of allergic disorders by inducing the migration of eosinophils towards inflammatory sites. The endocannabinoid system comprises the two known Gprotein coupled receptor CB1 and CB2, and a family of endogenous ligands. The CB1 receptor is predominantly expressed in the central nervous system, while CB2 receptors are mainly found in the immune system and in hematopoietic cells. Recently, GPR55 was identified as a new putative third cannabinoid receptor, which is expressed on a variety of cells, e.g. endothelial cells and neutrophils. In several studies L-α-lysophosphatidylinositol (LPI) was suggested as a potent endogenous agonist of this receptor. Lysophospholipids are involved in a variety of physiologic events, including platelet aggregation, vasopressor responses, wound healing, immune modulation and angiogenesis. In consideration of these facts, the specific aim of the present study is to investigate the impact of LPI and the GPR55 -agonist, AM251, on human eosinophil function. The effects of increasing concentrations of LPI and AM251 were determined with respect to flow cytometric Ca2+ flux and shape change responses as well as chemotaxis. In these assays I found that LPI does not elicit shape change, chemotaxis or Ca2+ flux responses in human eosinophils, but inhibits the stimulating effects of the potent eosinophil chemoattractant eotaxin. Moreover, it could be observed that AM251 does not induce nor inhibit eosinophil shape change, but mimics the effects of LPI on eosinophil Ca2+ flux and chemotactic responses. Due to the lack of selective GPR55 antagonists it still remains unclear whether these effects are GPR55 -mediated or not. Consequently, the aim of prospective studies is to confirm these findings and further analyze the effects of other GPR55 ligands.