SerpinB1 deficiency is not associated with increased susceptibility to pulmonary emphysema in mice

Cremona, Tiziana P.; Tschanz, Stefan A.; von Garnier, Christophe; Benarafa, Charaf (2013). SerpinB1 deficiency is not associated with increased susceptibility to pulmonary emphysema in mice. American journal of physiology - lung cellular and molecular physiology, 305(12), L981-L989. American Physiological Society 10.1152/ajplung.00181.2013

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Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and chronic bronchitis and is a leading cause of morbidity and mortality worldwide. Tobacco smoke and deficiency in α1-antitrypsin (AAT) are the most prominent environmental and genetic risk factors, respectively. Yet the pathogenesis of COPD is not completely elucidated. Disease progression appears to include a vicious circle driven by self-perpetuating lung inflammation, endothelial and epithelial cell death, and proteolytic degradation of extracellular matrix proteins. Like AAT, serpinB1 is a potent inhibitor of serine proteases including neutrophil elastase and cathepsin G. Because serpinB1 is expressed in myeloid and lung epithelial cells and is protective during lung infections, we investigated the role of serpinB1 in preventing age-related and cigarette smoke-induced emphysema in mice. Fifteen-month-old mice showed increased lung volume and decreased pulmonary function compared with young adult mice (3 mo old), but no differences were observed between serpinB1-deficient (KO) and wild-type (WT) mice. Chronic exposure to secondhand cigarette smoke resulted in structural emphysematous changes compared with respective control mice, but no difference in lung morphometry was observed between genotypes. Of note, the different pattern of stereological changes induced by age and cigarette smoke suggest distinct mechanisms leading to increased airway volume. Finally, expression of intracellular and extracellular protease inhibitors were differently regulated in lungs of WT and KO mice following smoke exposure; however, activity of proteases was not significantly altered. In conclusion, we showed that, although AAT and serpinB1 are similarly potent inhibitors of neutrophil proteases, serpinB1 deficiency is not associated with more severe emphysema.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Cremona, Tiziana Patrizia; Tschanz, Stefan A.; von Garnier, Christophe and Benarafa, Charaf

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1040-0605

Publisher:

American Physiological Society

Language:

English

Submitter:

Stefan Andreas Tschanz

Date Deposited:

01 Apr 2014 00:32

Last Modified:

29 Dec 2014 11:04

Publisher DOI:

10.1152/ajplung.00181.2013

PubMed ID:

24163143

Uncontrolled Keywords:

animal model cigarette smoke serpin

BORIS DOI:

10.7892/boris.40173

URI:

https://boris.unibe.ch/id/eprint/40173

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