NDLI: The pig as a model for investigating the role of neutrophil serine proteases in human inflammatory lung diseases

Content Provider	PubMed Central
Author	Bréa, Déborah François, Meurens Dubois, Alice V. Gaillard, Julien Claire, Chevaleyre Jourdan, Marie-lise Winter, Nathalie Brigitte, Arbeille Mustapha, Si-tahar Gauthier, Francis Attucci, Sylvie
Copyright Year	2012
Abstract	The serine proteases released by activated polymorphonuclear neutrophils [NSPs (neutrophil serine proteases)] contribute to a variety of inflammatory lung diseases, including CF (cystic fibrosis). They are therefore key targets for the development of efficient inhibitors. Although rodent models have contributed to our understanding of several diseases, we have previously shown that they are not appropriate for testing anti-NSP therapeutic strategies [Kalupov, Brillard-Bourdet, Dade, Serrano, Wartelle, Guyot, Juliano, Moreau, Belaaouaj and Gauthier (2009) J. Biol. Chem. 284, 34084–34091). Thus NSPs must be characterized in an animal model that is much more likely to predict how therapies will act in humans in order to develop protease inhibitors as drugs. The recently developed CFTR−/− (CFTR is CF transmembrane conductance regulator) pig model is a promising alternative to the mouse model of CF [Rogers, Stoltz, Meyerholz, Ostedgaard, Rokhlina, Taft, Rogan, Pezzulo, Karp, Itani et al. (2008) Science 321, 1837–1841]. We have isolated blood neutrophils from healthy pigs and determined their responses to the bacterial pathogens Pseudomonas aeruginosa and Staphylococcus aureus, and the biochemical properties of their NSPs. We used confocal microscopy and antibodies directed against their human homologues to show that the three NSPs (elastase, protease 3 and cathepsin G) are enzymatically active and present on the surface of triggered neutrophils and NETs (neutrophil extracellular traps). All of the porcine NSPs are effectively inhibited by human NSP inhibitors. We conclude that there is a close functional resemblance between porcine and human NSPs. The pig is therefore a suitable animal model for testing new NSP inhibitors as anti-inflammatory agents in neutrophil-associated diseases such as CF.
Related Links	http://dx.doi.org/10.1042/bj20120818
Ending Page	370
Page Count	8
Starting Page	363
File Format	PDF
ISSN	02646021
e-ISSN	14708728
Journal	Biochemical Journal
Issue Number	Pt 3
Volume Number	447
Language	English
Publisher	Portland Press Ltd.
Publisher Date	2012-11-01
Access Restriction	Open
Rights Holder	Portland Press Ltd.
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Biochemistry

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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