The smoking gun: Elastin fragments drive emphysema

Pulmonary emphysema is caused primarily by cigarette smoking, and the underlying cellular mechanisms are thought to involve smoke-induced activation of tissue degrading enzymes known as proteases. Elastases are proteases that specifically degrade the structural protein elastin and include enzymes such as MMP-12 (matrix metalloproteinase –12, also called macrophage metalloelastase), which is secreted by inflammatory cells called macrophages.

Now, researcher A. McGarry Houghton and colleagues at Harvard Medical School in Massachusetts, report that elastases cause emphysema in mice through the generation of pro-inflammatory elastin fragments.

The study appears online on February 9 in advance of print publication in the March issue of the Journal of Clinical Investigation. The authors found that mice that had inhaled pancreatic elastase or who were exposed to cigarette smoke developed elastin fragments in their lungs, macrophage accumulation, and emphysema. However, when the researchers blocked the activity of elastin fragments using a specific anti-elastin antibody, the macrophage numbers were reduced, and the emphysema was prevented in both models. Using cultured human monocytes (macrophage precursor cells), the authors demonstrate that elastin fragments are chemotactic, meaning that they are able to attract inflammatory cells.

The studies suggest that the degradation products of protease activity, in addition to the proteases themselves, may be promising targets for emphysema therapy.

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TITLE: Elastin fragments drive disease progression in a murine model of emphysema

AUTHOR CONTACT:
A. McGarry Houghton
Brigham and Women's Hospital, Boston, Massachusetts, USA
Phone: (617) 278-0765; Fax: (617) 232-4623; E-mail: mhoughton@rics.bwh.harvard.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=25617

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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