References
Query Results -- Details
MGI Accession ID: MGI:2680847
J Number: J:86599
Other Accession IDs:
Title: Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice.
Authors: Shapiro SD; Goldstein NM; Houghton AM; Kobayashi DK; Kelley D; Belaaouaj A
Journal: Am J Pathol
Volume: 163
Issue: 6
Date: 2003 Dec
Year: 2003
Pages: 2329-35
Review Status: Peer Reviewed
Abstract:
To address the role of neutrophil elastase in pulmonary emphysema, neutrophil elastase-deficient mice and wild-type littermate controls were exposed to long-term cigarette smoke. Compared to wild-type littermates, mice that were deficient in neutrophil elastase were significantly protected (59%) from the development of emphysema. Previously, we demonstrated complete protection from emphysema in the absence of macrophage elastase. Further analysis revealed several interactions between these two elastases. Each elastase inactivated the endogenous inhibitor of the other, with neutrophil elastase degrading tissue inhibitor of metalloproteinase-1, and macrophage elastase degrading alpha-1-antitrypsin. Cigarette smoke-induced recruitment of both neutrophils and monocytes was impaired in the absence of neutrophil elastase. Moreover, there was less macrophage elastase activity secondary to decreased macrophage accumulation in neutrophil elastase-deficient mice. This study demonstrates a direct role for neutrophil elastase in emphysema and highlights the interdependence of the proteinases and inflammatory cells that mediate lung destruction in response to cigarette smoke.
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