Human SLPI inactivation after cigarette smoke exposure in a new in vivo model of pulmonary oxidative stress

被引:47
作者
Cavarra, E
Lucattelli, M
Gambelli, F
Bartalesi, B
Fineschi, S
Szarka, A
Giannerini, F
Martorana, PA
Lungarella, G
机构
[1] Univ Siena, Dipartimento Fisiopatol & Med Sperimentale, I-53100 Siena, Italy
[2] Semmelweis Univ, Dept Med Chem Mol Biol & Pathobiochem, H-1444 Budapest, Hungary
关键词
antioxidant status; secretory leukoprotease inhibitor inactivation; bronchoalveolar lavage;
D O I
10.1152/ajplung.2001.281.2.L412
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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-PGF2(alpha). 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-2 alpha. 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.
引用
收藏
页码:L412 / L417
页数:6
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