Elastase inhibitory activity of airway α1-antitrypsin is protected by treatment with a catalytic antioxidant in a baboon model of severe bronchopulmonary dysplasia.

Published

Journal Article

Recent studies in animal models of bronchopulmonary dysplasia (BPD) suggest that antioxidant treatments may be beneficial for the disease. However, the mechanisms by which these drugs improve the course of BPD are not completely known. Alpha1-antitrypsin (α1-AT) is one of the major serine protease inhibitors in human plasma that has antielastase and antiapoptotic activities. Both activities of α1-AT are dependent on its reactive site loop (RSL), which is highly susceptible to oxidative inactivation. In this study, we investigated the elastase inhibitory activity of α1-AT in two different baboon models of BPD, the "new BPD" and the "severe BPD" models, and determined the effect of treatment with a catalytic antioxidant, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP), on the elastase inhibitory activity of α1-AT in the severe BPD model. Our results demonstrate the presence of sufficient elastase inhibitory activity of the airway α1-AT in the new but not in the severe BPD model. Treatment of severe BPD group baboons with the catalytic antioxidant MnTE-2-PyP resulted in augmentation of the elastase inhibitory activity of α1-AT. These findings suggest that prevention of the oxidative inactivation of α1-AT may be one of the mechanisms by which antioxidant therapy improves the pulmonary outcomes in animal models of severe BPD.

Full Text

Cited Authors

  • Karaaslan, C; Hirakawa, H; Yasumatsu, R; Chang, L-YL; Pierce, RA; Crapo, JD; Cataltepe, S

Published Date

  • October 2011

Published In

Volume / Issue

  • 70 / 4

Start / End Page

  • 363 - 367

PubMed ID

  • 21705962

Pubmed Central ID

  • 21705962

Electronic International Standard Serial Number (EISSN)

  • 1530-0447

International Standard Serial Number (ISSN)

  • 0031-3998

Digital Object Identifier (DOI)

  • 10.1203/PDR.0b013e31822a357e

Language

  • eng