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Pathogenetic significance of reactive oxygen species in diffuse fibrosing alveolitis
1Pneumologische Abteilung, Universitt Müchen, Germany.
Abstract:
Excessive release of reactive oxygen metabolites (ROM) from lung inflammatory cells has been claimed to be of major pathogenetic significance in diffuse fibrosing alveolitis. In the present study, the content of oxidized methionine residues [Met(O)] as a percentage of total methionine (Met) in BAL-derived proteins was used to assess the biologic effect of ROM. In addition, procollagen-III-peptide was measured in BAL fluid as a marker of fibroblast activation. We investigated bronchoalveolar lavage (BAL) samples from seven control patients without evidence of interstitial lung disease and from 42 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (IPF), n = 20, or by collagen vascular disease (CVD), n = 22. Met(O) was elevated in the patients with IPF or CVD compared with that in the control subjects (8.86 +/- 1.26 and 8.13 +/- 1.44% versus 3.36 +/- 0.49%, p less than 0.01 and p less than 0.05, respectively; mean +/- SEM). A positive correlation was found between percentage of neutrophils in BAL and Met(O) in both groups separately and combined (IPF, r = 0.84; p less than 0.001; CVD, r = 0.44; p less than 0.05; IPF and CVD, r = 0.60; p less than 0.001), whereas an inverse relationship existed between Met(O) and the percentage of alveolar macrophages in BAL (IPF, r = -0.59; p less than 0.01; CVD, r = -0.24; NS; IPF and CVD, r = -0.41; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Oxidative stress, measured by oxidized methionine in bronchoalveolar lavage (BAL) proteins, is elevated in patients with fibrosing alveolitis. This elevation correlates with increased neutrophils and decreased macrophages, indicating significant lung inflammation.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Pathophysiology
Background:
- Diffuse fibrosing alveolitis is linked to reactive oxygen metabolite (ROM) release from lung inflammatory cells.
- Assessing ROM's biological impact is crucial for understanding alveolitis pathogenesis.
- Oxidized methionine (Met(O)) in bronchoalveolar lavage (BAL) proteins serves as a marker for ROM activity.
Purpose of the Study:
- To evaluate the levels of oxidized methionine (Met(O)) in BAL proteins as a measure of ROM effects in fibrosing alveolitis.
- To assess procollagen-III-peptide as a marker of fibroblast activation in these patients.
- To investigate the relationship between Met(O) levels and inflammatory cell populations in BAL.
Main Methods:
- Analyzed BAL samples from 7 control subjects and 42 patients with fibrosing alveolitis (idiopathic pulmonary fibrosis [IPF] and collagen vascular disease [CVD]).
- Quantified Met(O) as a percentage of total methionine (Met) in BAL-derived proteins.
- Measured procollagen-III-peptide in BAL fluid.
- Correlated Met(O) levels with the percentages of neutrophils and alveolar macrophages in BAL.
Main Results:
- Met(O) levels were significantly higher in patients with IPF (8.86 ± 1.26%) and CVD (8.13 ± 1.44%) compared to controls (3.36 ± 0.49%).
- A positive correlation was observed between BAL neutrophils and Met(O) levels across all patient groups.
- An inverse relationship was found between BAL alveolar macrophages and Met(O) levels.
Conclusions:
- Elevated Met(O) in BAL proteins indicates increased oxidative stress in fibrosing alveolitis.
- Neutrophil abundance in BAL is associated with higher Met(O) levels, suggesting their role in ROM production.
- Reduced alveolar macrophages correlate with increased oxidative stress in fibrosing alveolitis.