Abstract
Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens from adult CF patients were analyzed for MPO characteristic protein modifications and found to contain large amounts of active MPO as well as high levels of protein-associated 3-chlorotyrosine and 3,3'-dityrosine, products that result from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum levels of nitrite (NO2/-) and nitrate (NO3/-), indicating local production of nitric oxide (NO·), were not elevated but in fact were slightly reduced in CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in CF sputum compared with controls, reflecting the formation of reactive nitrogen intermediates, possibly through MPO-catalyzed oxidation of NO2/-. CF sputum MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured tracheobronchial epithelial cells; however, peroxidase-dependent protein oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and perhaps formation of secondary cytotoxic products within CF sputum. Our findings demonstrate the formation of MPO-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF, which collectively may contribute to bronchial injury and respiratory failure in CF.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 279 |
| Issue number | 3 23-3 |
| State | Published - 2000 |
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Keywords
- 3,3'-dityrosine
- 3-chlorotyrosine
- 3-nitrotyrosine
- Hypochlorous acid
- Inflammation
- Nitric oxide
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cell Biology
- Physiology
- Physiology (medical)
Cite this
Myeloperoxidase and protein oxidation in cystic fibrosis. / Van Der Vliet, Albert; Nguyen, Mai N.; Shigenaga, Mark K.; Eiserich, Jason P.; Marelich, Gregory P.; Cross, Carroll E.
In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 279, No. 3 23-3, 2000.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Myeloperoxidase and protein oxidation in cystic fibrosis
AU - Van Der Vliet, Albert
AU - Nguyen, Mai N.
AU - Shigenaga, Mark K.
AU - Eiserich, Jason P.
AU - Marelich, Gregory P.
AU - Cross, Carroll E
PY - 2000
Y1 - 2000
N2 - Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens from adult CF patients were analyzed for MPO characteristic protein modifications and found to contain large amounts of active MPO as well as high levels of protein-associated 3-chlorotyrosine and 3,3'-dityrosine, products that result from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum levels of nitrite (NO2/-) and nitrate (NO3/-), indicating local production of nitric oxide (NO·), were not elevated but in fact were slightly reduced in CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in CF sputum compared with controls, reflecting the formation of reactive nitrogen intermediates, possibly through MPO-catalyzed oxidation of NO2/-. CF sputum MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured tracheobronchial epithelial cells; however, peroxidase-dependent protein oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and perhaps formation of secondary cytotoxic products within CF sputum. Our findings demonstrate the formation of MPO-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF, which collectively may contribute to bronchial injury and respiratory failure in CF.
AB - Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens from adult CF patients were analyzed for MPO characteristic protein modifications and found to contain large amounts of active MPO as well as high levels of protein-associated 3-chlorotyrosine and 3,3'-dityrosine, products that result from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum levels of nitrite (NO2/-) and nitrate (NO3/-), indicating local production of nitric oxide (NO·), were not elevated but in fact were slightly reduced in CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in CF sputum compared with controls, reflecting the formation of reactive nitrogen intermediates, possibly through MPO-catalyzed oxidation of NO2/-. CF sputum MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured tracheobronchial epithelial cells; however, peroxidase-dependent protein oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and perhaps formation of secondary cytotoxic products within CF sputum. Our findings demonstrate the formation of MPO-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF, which collectively may contribute to bronchial injury and respiratory failure in CF.
KW - 3,3'-dityrosine
KW - 3-chlorotyrosine
KW - 3-nitrotyrosine
KW - Hypochlorous acid
KW - Inflammation
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=0033830339&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033830339&partnerID=8YFLogxK
M3 - Article
C2 - 10956629
AN - SCOPUS:0033830339
VL - 279
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 3 23-3
ER -