Wirkung von Carbon Black Nanopartikeln (CBNP) auf die Funktion von Typ II Pneumozyten

Nachhaltige Schädigungen der Lungen durch den Eintrag von Schadstoffen über die Außenluft sind unumstritten. In den letzten Jahrzehnten konnte der Eintrag größerer Schadstoffmengen in die Umwelt in Industrieländern wie Deutschland enorm verringert werden. Dennoch kommt es immer wieder zu Überschreit...

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Bibliographic Details
Main Author: Schreiber, Nicole
Contributors: Müller, B. (Prof. Dr.) ; Bauer, S. (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2015
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Sustained damages of lungs caused by the inhalation of air pollutants are undisputed. Within the last decades in industrialized countries like Germany the emission of harmful substances has been greatly reduced. Nevertheless, repeated exceedances of maximum limits for particulate matter in urban areas have been measured. Currently complicated particle analyses prevent comprehensive examinations of the fine particle fraction composition in the air. In addition the increasing use of functionalized CBNP in numerous fields of daily life increases the risk of unwanted release into the environment and the outcome of lung diseases. Hence the toxicological potential of CBNP on the terminal region of the lung has been analyzed using BALB/c mice and non-functionalized (Pr907μg-BSA, Pr907μg+BSA), surface-functionalized (NA-Pr907μg+BSA, BaP- Pr907μg+BSA, PAH-AR7μg+BSA) and surface-adjusted CBNP (PAK-AR15μg+BSA), reference particles (DQ127μg-BSA) and several negative controls (NaCl70μl-BSA, H2O70μl-BSA, H2O70μl+BSA). The administrations of the suspensions were done by oropharyngeal aspiration. Pulmonary function measurements were performed after a particle retention time of 2 days by noninvasive head-out body plethysmography. On day three lungs were taken for histological examinations and type II pneumocyte isolation. Parallel to cell isolations BAL were collected. On the basis of a first experiment, the optimal particle retention time of 3 days was determined. During the use of different CBNP in short-term experiment, no massive structural changes or functional limitations of the terminal respiratory tract by surface non-functionalized and functionalized particles could be observed. This argues for an effective particle clearance by macrophages within the alveolar region. However, there were also indications of lung homeostasis disturbance. In particular, the mRNA-expression of various antioxidants, as well as the expression of surfactant proteins and key enzymes of surfactant synthesis revealed scattered deviations from the controls. The results of the multiple applications of non-functionalized CBNP during the long-term exposure indicate a more limited clearance. As reflected by increased collagen deposits along the bronchioles and blood vessels and increased protein and phospholipid concentrations in BAL-samples after multiple Pr907μg-BSA aspiration towards the H2O70μl-BSA negative control. Recurring reports of harmful air contaminations and the growing market for carbon-based NP require further toxicological assessments and development of existing measurement and analysis for environmental samples. Further tests with multiple oropharyngeal aspirations of low doses surface functionalized CBNP are needed to assess long-term effects. In addition to structural and functional changes in the lungs these toxicological evaluations have to verify the translocation of chemically functionalized CBNP to other organs and translocation associated effects. Further the increasing number of lung diseases in the population makes it necessary to include investigations on pre-damaged lungs. Another challenge of future studies will be the determination of precise interactions between chemical functionalized particle surfaces and biological fluids to get information about basic in vivo mechanisms.