Human SLPI inactivation after cigarette smoke exposure in a new in vivo model of pulmonary oxidative stress.
Am J Physiol Lung Cell Mol Physiol
; 281(2): L412-7, 2001 Aug.
Article
en En
| MEDLINE
| ID: mdl-11435216
The role of oxidative stress in inactivating antiproteases is the object of debate. To address this question, we developed an in vivo model of pulmonary oxidative stress induced by cigarette smoke (CS) in mice. The major mouse trypsin inhibitor contrapsin is not sensitive to oxidation, and the mouse secretory leukoprotease inhibitor (SLPI) does not inhibit trypsin. Instead, human recombinant (hr) SLPI inhibits trypsin and is sensitive to oxidation. Thus we determined the effect of CS in vivo on hrSLPI antiproteolytic function in the airways of mice. CS caused a significant decrease in total antioxidant capacity in bronchoalveolar lavage fluid (BALF) and significant changes in oxidized glutathione, ascorbic acid, protein thiols, and 8-epi-PGF(2alpha). Intratracheal hrSLPI significantly increased BALF antitryptic activity. CS induced a 50% drop in the inhibitory activity of hrSLPI. Pretreatment with N-acetylcysteine prevented the CS-induced loss of hrSLPI activity, the decrease in antioxidant defenses, and the elevation of 8-epi-PGF-(2alpha). Thus an inactivation of hrSLPI was demonstrated in this model. This is a novel model for studying in vivo the effects of CS oxidative stress on human protease inhibitors with antitrypsin activity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plantas Tóxicas
/
Humo
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Nicotiana
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Proteínas
/
Serpinas
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Estrés Oxidativo
/
Exposición a Riesgos Ambientales
/
Pulmón
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos