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.

肥大细胞是过敏性炎症反应的主要效应细胞类型。传统上认为，通过抗原和抗原特异性IgE结合其高亲和力受体Fc¿RI激活肥大细胞是最常见和医学上重要的肥大细胞激活机制。这一机制在过去已被广泛研究，但最近的一些观察表明，其他因素也能够通过作用方式调节肥大细胞的激活，虽然尚未得到很好的理解，但可能在炎症过程中调节肥大细胞功能方面发挥重要作用。在具有这些特性的因子中，内皮素-1 (ET-1) - ETA的g蛋白偶联受体（GPCR）和趋化因子受体CCR3被认为是有希望进一步研究的候选者。主要目标是探索这两种gpcr和Fc - RI之间是否存在关系，通过协同工作，导致肥大细胞作为效应细胞和免疫调节细胞的“微调”。此外，我们将在体内小鼠模型中研究CCR3或ETA与Fc¿RI之间相互作用在皮肤过敏反应中的相关性。为此，将缺乏CCR3、ETA或Fc¿RI的正常或基因工程肥大细胞注射到肥大细胞基因缺乏的小鼠的耳朵中。在过敏反应或GPCR配体依赖性反应开始后，将通过测量耳部肿胀量来量化炎症程度的差异。如果我们证实gpcr和Fc¿RI之间存在功能显著的相互作用，并证明它们对过敏或gpcr诱导炎症的发生和进展的重要性，这将为开发治疗过敏的替代疗法提供有希望的基础。

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.