'Smoking Gun' Behind Emphysema Identified
TUESDAY, Feb. 14 (HealthDay News) -- Matrix metalloproteinase-12 (MMP-12), one of the enzymes that degrades the structural protein elastin, may contribute to emphysema by generating pro-inflammatory elastin fragments that attract monocytes to the lung, according to a study in mice published online Feb. 9 in the Journal of Clinical Investigation.
A. McGarry Houghton, M.D., of Harvard Medical School in Boston, and colleagues studied wild-type and MMP-12-deficient mice that were exposed to cigarette smoke. Previous studies have shown that MMP-12-deficient mice are resistant to emphysema when exposed to cigarette smoke.
Bronchoalveolar lavage fluid showed that the wild-type mice, but not MMP-12-deficient mice, had elastin fragments in their lungs and chemotactic activity for monocytes in vitro. When the activity of elastin fragments was blocked with an anti-elastin antibody, it reduced monocyte recruitment.
"Although the findings here are limited to a model of emphysema, the concept that degradation products of elastin can drive a macrophage-predominant, chronic inflammatory disease process is potentially applicable to all diseases that occur in elastin-rich organs, including coronary artery disease, peripheral vascular disease and aortic aneurysm," the authors state.
