Abstract (deu)
Annexin A8 (AnxA8) is the eighth member of the Ca2+/phospholipid (PL) binding annexin family. Annexins are known to be ubiquitous and abundant membrane-binding proteins. As membrane-binding proteins, annexins function as membrane organizers and targeting proteins of various processes, thereby they participate in the assembly of enzyme and signalling complexes, vesicle trafficking and repair. Less is known about AnxA8; it specifically binds to phosphatidylinositol- 4,5-bisphosphate (PIP2), F-Actin and associates with late endosomes (LE), which suggests its role in the regulation of epidermal growth factor receptor (EGFR) and/or endocytic transport. In contrary to other annexins, AnxA8 is a less ubiquitous and generally low expressed protein, reflecting its tissue-specific function. AnxA8 was found to be upregulated in different cancer types, like pancreatic cancer or breast cancer. Since most cancer types indicate a deficient EGFR, a correlation between AnxA8 and EGFR is speculated. This study focused on the specific role of AnxA8 in lung, which represents one of the AnxA8-positive localizations. In fact, the expression and cellular localization of AnxA8 was investigated in normal lung, lung cancer (adenocarcinoma and squamous-cell carcinoma), (lipopolysachharides (LPS), lipopeptide (PAM3) and the glucocorticoid analogue dexamethasone (DEXA)) stimulated lung, and pathogen-infected lung tissues. In addition, the expression was examined in bronchoalveolar lavage cells (BALs) of chronic obstructive pulmonary disease patients and LPS/PAM3 stimulated A549 cells. Simultanously, all samples were compared to EGFR using immunohistochemistry, RT-PCR and western blot techniques. IHC results show a membrane-bound localization of both AnxA8 and EGFR, although the expression of AnxA8 appeared lower. AnxA8 was predominantly found in alveolar macrophages and epithelial cells type II (possibly in alveolar epithelial cells type I as well). Stimulation by DEXA affected the expression of AnxA8 in lung, indicated by increased signals in alveolar macrophages. An increased expression in inflammatory cells could also been detected in BAL cells of COPD patients.