Oxidative Modifikationen des bronchoalveolären Proteoms und der Surfactant Proteine A und D bei chronischen Lungenerkrankungen
Beschreibung
vor 20 Jahren
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.
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.
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