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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)

We studied the reparative process after inhalation exposure to 20 ppm of nitrogen dioxide (NO2) in the lungs of hemizygous blotchy male (Blo/g) and heterozygous blotchy female (Bio/+) mice. Age-matched siblings (C3Hf) without the blotchy gene at X-chromosome locus (+/y) and +/+) served as control animals. After exposure to NO2 for 28 days, there was a marked progression in the extent of emphysema in Blo/y mice associated with a significant decrease of internal surface area (p < 0.05) and an increase in the mean linear intercept (p < 0.005). In contrast, +/y, Blo/+, and +/+ mice showed mild airspace enlargement without decrease in internal surface area after similar exposures. Blo/y mice killed 1 month after cessation of NO2 exposure showed a persistent, mild chronic bronchiolitis that was more frequent and of greater severity than that present in control +/y mice. Alveolar macrophages in the Blo/y mice were larger than those in +/y, +/+, and Blo/+ mice both before and after exposure to NO2. Crystalloid inclusions were observed in the enlarged alveolar macrophages of the Blo/g mice only after exposure to NO2, but were not seen in control animals. These observations indicate that the pattern of lung injury and repair after subacute exposure to 20 ppm of NO2 in the Blo/y mouse differs from that present in age-matched siblings in that inherited abnormalities in alveolar macrophage function may exist in addition to the previously described alterations in connective tissue proteins. Both of these alterations may influence the development of emphysema in the blotchy male mouse.