Andreas Hector, MD
Role of Bronchial Epithelial Cells in Alpha-1-Antitrypsin Deficiency
Primary AAT Deficiency is the leading cause of early pulmonary emphysema and liver disease among Caucasians, whereas secondary AAT deficiency is critical for the pathogenesis of cystic fibrosis (CF) and many other bronchiectatic pulmonary diseases. Recently, AAT has been shown to evoke anti-inflammatory actions which might be independent of the inhibition of neutrophil elastase. Direct effects of AAT on various intracellular signaling pathways have also been observed. If such functions of AAT are truly active also in pulmonary epithelial cells, new avenues for early and preventive treatment with inhaled AAT may open and will help to prevent pulmonary damage in the broad range of pulmonary diseases.
As a sequel of our laboratory's work we will address the following hypothesis: (1) is the pro-inflammatory activity of epithelial cells, either normal cells (not activated) or endogenously activated through their endoplasmatic reticulum stress response due to their CFTR mutation, regulated by exogenous AAT; (2) is the epithelial cell-induced inflammation and apoptosis in presence or absence of stimuli and stress factors significantly blocked by functionally active AAT, and lastly (3) can all key effects observed in these in vitro experiments be re-capitulated in epithelial cells ex vivo, obtained by nasal epithelial brush from patients with cystic fibrosis.
We propose that bronchial epithelial cells play an eminent role in the pathogenesis of lung diseases with primary or secondary AAT Deficiency states. AAT may be capable to attenuate the pro-inflammatory activity and apoptosis not only by inhibition of extracellular proteases but also very early by direct interaction with epithelial cells. This may open novel treatment options.
Curriculum Vitae of Andreas Hector
Since 2007, Dr. Andreas Hector is with the Department of Pediatric Pneumology at the Children's Hospital of the Ludwig- Maximilians-University of Munich. After taking the preliminary medical examination at the Friedrich-Alexander-University of Erlangen / Nürnberg in 2002, he graduated from the Medical School of the Ludwig- Maximilians-University of Munich in 2006. He earned his M.D. degree with magna cum laude from the Clinical Cooperation Group "Pediatric Immune Regulation" of the Ludwig-Maximilians-University of Munich. In his thesis, he focused on the association of signaling receptors and allergic responses in pregnant women and their offspring.
Currently, Dr. Hector is involved in a randomized, placebo-controlled, doubleblind study. This clinical phase II trial investigates the effects of inhaled glutathione in cystic fibrosis patients with regards to clinical outcomes and defined markers in induced sputum concerning i. e. inflammation, apoptosis and oxidative state.
Andreas Hector, MD
Research Center Kubus
Children's Hospital of the University of Munich