The Journal of Experimental Medicine
ThymUS '08
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Published online June 30, 2008
doi:10.1084/jem.20072080
The Journal of Experimental Medicine, Vol. 205, No. 7, 1529-1534
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Gooptu et al.
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*Emphysema
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COMMENTARY

 Polymers and inflammation: disease mechanisms of the serpinopathies

Bibek Gooptu and David A. Lomas

B.G. is at School of Crystallography, Birkbeck College, University of London, London WC1E 7HX, England, UK
D.A.L. is at Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 OXY, England, UK

CORRESPONDENCE D.A.L.: dal16{at}cam.ac.uk


ABSTRACT
Members of the serpin (serine proteinase inhibitor) superfamily play a central role in the control of inflammatory, coagulation, and fibrinolytic cascades. Point mutations that cause abnormal conformational transitions in these proteins can trigger disease. Recent work has defined three pathways by which these conformers cause tissue damage. Here, we describe how these three mechanisms can be integrated into a new model of the pathogenesis of emphysema caused by mutations in the serpin {alpha}1-antitrypsin.


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