Bedeutung der Interaktion von G-Protein gekoppelten Rezeptoren und dem Fcepsilon-Rezeptor I für die Feinregulation der Mastzellaktivierung und darüber hinaus für die Entstehung und das Fortschreiten entzündlicher Prozesse in der Haut untersucht werden.

点击翻译按钮获取中文摘要

Mast cells are the major effector cell type in allergic inflammatory reactions. Traditionally, it is thought that mast cell activation via antigen and antigenspecific IgE binding to its high-affinity receptor Fc¿RI represents the most common and medically important mechanism of mast cell activation. This mechanism has been studied extensively in the past, but recently several observations indicate that other factors are able to modulate mast cell activation by modes of action, which, while not well understood, nevertheless may play an important role in regulating mast cell function during inflammatory processes. Among factors, which exhibit those properties, the G-protein coupled receptor (GPCR) for endothelin-1 (ET-1) ETA as well as the chemokine receptor CCR3 were identified as promising candidates for further study. The main goal is to explore whether there is a relationship between those two GPCRs and the Fc¿RI, which, by working in concert, result in the ¿fine-tuning¿ of mast cells as effector and immunoregulatory cells. Moreover, we will investigate the relevance of interactions among the CCR3 or ETA and the Fc¿RI in allergic reactions of the skin in a mouse model in vivo. For this purpose, either normal or genetically engineered mast cells lacking CCR3, ETA or Fc¿RI, will be injected into the ears of mice that are genetically deficient in mast cells. After initiation of an allergic or a GPCR ligand-dependent response, differences in the degree of inflammation will be quantified by measuring the amount of ear swelling. If we confirm the existence of functionally significant interactions between GPCRs and the Fc¿RI, and demonstrate their importance for the development and progression of allergic or GPCR-induced inflammation, this would provide a promising basis for the development of alternative therapies for the treatment of allergies.