Matrix metalloproteinase 9 (MMP9) and MMP12, two elastolytic proteinases, and MMP1 (a nonelastolytic collagenase) have been implicated in the pathogenesis of emphysema. We sought to determine whether mRNA levels in alveolar macrophages (AMs) and genetic polymorphisms of these MMPs are related to the presence of emphysema in patients undergoing lung resection for localized lung cancers. AMs were recovered by bronchoalveolar lavage of resected lung segments uninvolved by tumor in 54 subjects, and purified by Hypaque-Ficoll centrifugation. We determined mRNA expression of these three proteinases in freshly lavaged AMs and in AMs cultured without and with stimulation by LPS, interleukin 1, and tumor necrosis factor for 24 and 48 hr. Levels of mRNA levels were measured using real-time polymerase chain reaction with a LightCycler (Roche Molecular Systems, Alameda, CA). The subjects were genotyped for the following MMP promoter polymorphisms: MMP1 G-1607GG, MMP9 C-1562T, and MMP12 A-82G.

MMP1 mRNA in uncultured AMs was significantly related to the extent of emphysema by computed tomography (CT) scan of the chest (p 0.001), but there was no significant relation between MMP9 and MMP12 mRNA and emphysema. The MMP9 C-to-T single-nucleotide polymorphism (C-1562T) significantly influenced MMP9 mRNA expression in AMs (p 0.04), and an MMP9 CA repeat was significantly related to CT assessment of emphysema (p 0.01). Our findings support a pathogenic role for MMP1 in human emphysema; in addition, genetic polymorphisms in MMP9 may have a pathogenic effect.