Increased levels of oxidized methionine residues in bronchoalveolar lavage fluid proteins from patients with idiopathic pulmonary fibrosis.
Phagocytic cells are believed to play a crucial role in the development of inflammatory lung diseases. We assumed that the oxidation of methionine (met) to methionine sulfoxide [met(O)] by oxygen-derived free radicals released from phagocytes is one parameter to identify the oxidative mechanisms of lung injury. To test this hypothesis we determined the molar ratio of met(O)/met in the soluble protein fraction of bronchoalveolar lavage (BAL) fluids from healthy nonsmokers and from nonsmoking patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. The met(O)/met ratio of the healthy nonsmoker group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). In contrast, the met(O)/met ratio of the nonsmoking IPF group (n = 11) was significantly increased to 0.223 +/- 0.053 (p less than 0.0002). The BAL fluids of this group showed strongly increased numbers of neutrophils but normal numbers of alveolar macrophages (AM). In the sarcoidosis group (n = 10) the met(O)/met ratio (0.048 +/- 0.010) was not significantly different from control values. A close relationship was found between the met(O)/met ratios and the relative as well as the absolute neutrophil counts (r = 0.86; p less than 0.0002; n = 22). In contrast, no significant correlation was found between the met(O)/met ratios and the absolute AM counts (r = 0.22; p = 0.32; n = 22). We conclude that mechanisms of oxidative lung injury in IPF can be characterized by oxidation of met and that this oxidation may be mediated by neutrophils.
Maier
K
K
Projekt Inhalation der Gesellschaft für Strahlen- und Umweltforschung München, Neuherberg, FRG.
Leuschel
L
L
Costabel
U
U
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000378:metabolism*; D004350:Drug Residues; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D012507:Sarcoidosis / Q000378:metabolism / Q000473:pathology
D011506:Proteins; D008715:Methionine; C013111:methionine sulfoxide