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Starosta, Vitaliy (2004): Oxidative Modifikationen des bronchoalveolären Proteoms und der Surfactant Proteine A und D bei chronischen Lungenerkrankungen. Dissertation, LMU München: Medizinische Fakultät



Bronchoalveolar lavage (BAL) liquid of 138 children with different inflammatory lung diseases was examined to determine the magnitude of the oxidative stress in the lungs. The content of protein carbonyls was measured by means of a sensitive dot-blot assay as a parameter of protein oxidation. The oxidative stress was highest in the group of the patients with cystic fibrosis (CF). In these patients direct correlations existed between the magnitude of protein oxidation and the content of neutrophil granulocytes in the BAL as well as a reverse proportionality between lung function and protein oxidation. The pattern of distribution and the sensitivity of different proteins to oxidation were determined in samples with different degree of oxidation by means of the 2-D-electrophoresis. Plasma proteins present in BAL fluid, e.g. albumin and transferrin, were especially sensitive to oxidation. Oxidation of the SP-D primary chain was achieved only by relatively strong oxidation in vitro. In contrast to SP-D, SP-A was very sensitive to the oxidative stress. The influence of antioxidative therapy with inhaled glutathione was examined in CF patients by measurement of protein carbonyls, protein thiols and lipid hydroperoxyds in BAL fluid before and after the therapeutic intervention. GSH inhaled for two weeks had no effect on the parameters assessed. Even if the primary chain of SP-D was very resistant towards oxidative influences, oxidation caused nevertheless clear changes of the macromolecular organization of SP-D. It led to the depolimerisation of the SP-D structure which is usually supported by disulfid bridges. SP-D damaged in this way had lost essential functional properties and was no more capable to agglutinate bacteria. Local oxidative stress plays an important role in different lung diseases in childhood and is especially pronounced in the presence of chronic, neutrophilic inflammation. Successful specific therapeutic interventions are nowadays not easily realized.