**5.2.2 Matrix metalloproteinases (MMPs)**

MMPs are a family of 24 enzymes that require coordination of zinc at the active site, have overlapping substrate specificity, and are inhibited by TIMPs(Parks & Shapiro,2001 as cited in Shapiro SD,2010). Several MMPs degrade elastin and contribute to emphysema including MMP-2, MMP-9 (gelatinase A and B), MMP-7 (matrilysin), and MMP-12 (macrophage elastase). MMP-1, -8, -13 are also collagenases, and thus degrade another critical matrix component.

Several MMPs have been associated with human COPD including MMP-1, MMP-9, MT1- MMP, and MMP-12(Imai et al.,2001;Molet et al.,2005;Russell et al.,2002 as cited in Shapiro SD,2010). Macrophages have the capacity to produce MMP-1, MMP-3, MMP-7, MMP-9, MMP-12, and MMP-19. MMP-12 is one of the most highly up-regulated genes in macrophages of human smokers(Atkinson & Senior,2003 as cited in Shapiro SD,2010). Role of MMPs in COPD pathogenesis is further supported by the epidemiologic prevalence of polymorphisms of MMP in caucasian COPD patients(Hunninghake et al.,2009 as cited in Shapiro SD,2010).
