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Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity.
Open accessAbstract
The elastase inhibitory capacity per mg of alpha 1-proteinase inhibitor (alpha 1 PI) was measured in the bronchoalveolar lavage (BAL) fluid from 26 healthy smokers and 24 nonsmokers. Activity was decreased by 40% in smokers' BAL fluid compared to nonsmokers. This effect was demonstrable by using human neutrophil elastase as well as porcine pancreatic elastase as test enzyme (elastase, EC 3.4.21.11) and was reproducible when selected individuals in each group underwent lavage on repeated occasions. In contrast, the functional activity of alpha 1-antichymotrypsin was not decreased in smokers' BAL fluid. Crossed antigen-antibody electrophoresis confirmed that inactivation of alpha 1 PI was responsible for the decrease in the elastase inhibitory capacity of smokers' BAL fluid. alpha 1 PI purified from smokers' BAL fluids contained methionine sulfoxide (4 mol/mol of inactive alpha 1 PI), whereas alpha 1 PI from nonsmokers' BAL fluid did not. Smokers' alpha 1 PI was indistinguishable from nonsmokers' alpha 1 PI on the basis of electrophoretic mobility, molecular weight, and immunoreactivity. Thus, oxidation of methionine residues in lung alpha 1 PI is associated with cigarette smoking. Because chemical oxidation of alpha 1 PI in vitro causes loss of its elastase inhibitory activity, the present observations suggest that methionine oxidation may also be the cause of decreased functional activity of lung alpha 1 PI in smokers. Oxidative inactivation of alpha 1 PI in the lungs of cigarette smokers may play a role in the development of pulmonary emphysema in this group.
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Cited by
Vestbo, J., Hurd, S. S., Agustí, A. G., Jones, P. W., Vogelmeier, C., Anzueto, A., Barnes, P. J., Fabbri, L. M., Martinez, F. J., Nishimura, M., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201204-0596pp · Cited by 15,983
Radical-free biology of oxidative stress
Jones, D. P. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00283.2008 · Cited by 1,213
Macrophages and Polymorphonuclear Neutrophils in Lung Defense and Injury
Sibille, Y., & Reynolds, H. Y. (1990) · American Review of Respiratory Disease · doi:10.1164/ajrccm/141.2.471 · Cited by 1,083
Clinical Relevance of Biomarkers of Oxidative Stress
Frijhoff, J., Winyard, P. G., Zarkovic, N., Davies, S. S., Stocker, R., Cheng, D., Knight, A. R., Taylor, E. L., Oettrich, J., Ruskovska, T., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6317 · Cited by 909
Oxidation of methionyl residues in proteins: Tools, targets, and reversal
Vogt, W. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)00158-g · Cited by 883
Metadata
- Authors
- Carp, H., Miller, F., Hoidal, J. R., & Janoff, A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1982-03
- Volume
- 79
- Issue
- 6
- Pages
- 2041-2045
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2024182441
- Cited by
- 343
- References
- 0
- FWCI
- 26.73
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. https://app.cochat.ai/papers/10.1073/pnas.79.6.2041
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- Carp, H., Miller, F., Hoidal, J. R., & Janoff, A. (1982). Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.79.6.2041
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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