Regulierung von Immun- und Reparaturprozessen am pulmonalen Atemwegsepithel durch Adrenomedullin in Bezug auf Asthma bronchiale

This dissertation was conducted in the Department of Clinical Chemistry and Molecular Diagnostics // The asthmatic airway epithelium is fundamentally abnormal in structure and function and reacts more sensitively to a variety of airway components. One difference is a reduced epithelial expression of the endogenous regulatory peptide adrenomedullin (AM), for reasons yet unknown. In regard of AM as a potential new therapeutic target in bronchial asthma, the aim of this doctoral thesis was to determine the role of AM in inflammatory and wound healing processes of the human airway epithelium. In vitro examinations of immortalized human bronchial epithelial (HBE) and alveolar A549 cells showed that AM significantly accelerates wound closure and cell migration but leaves no impact on the levels of cytokines or cell adhesion molecules. The results match further data of our working group which show unchanged levels of inflammatory markers in serum and bronchoalveolar lavage after intranasal application of AM in an acute OVA mouse model of allergic airway, while hyperreagibility and plasma extravasation of the airway mucosa are significantly reduced (Hagner H, Welz H, Kicic A, et al. (2012): Suppression of adrenomedullin contributes to vascular leakage and altered epithelial repair during asthma. Allergy 67:998-1006). Regarding this data in conjunction with further publications discussed within the dissertation, AM offers a promising new therapeutic target in bronchial asthma. Its application should be further evaluated in asthmatic patients within clinical studies.