The role of metalloelastase in immune complex-induced acute lung injury

Matrix metalloproteases (MMPs) are a group of zinc-dependent endopeptidases that can degrade every component of the extracellular matrix. Under normal circumstances, the levels of MMPs are tightly regulated at both transcript ional and posttranscriptional levels. However, they are up-regulated in pat hological states such as inflammation. Previous investigations have suggest ed that MMP-12 (metalloelastase) may be an important mediator in the pathog enesis of chronic lung injury. In this study we investigated the role of me talloelastase in the pathogenesis of acute lung injury using mice containin g a targeted disruption of the metalloelastase gene. Neutrophil influx into the alveolar space in metalloelastase-deficient animals was reduced to sim ilar to 50% of that observed in parent strain mice following the induction of injury by immune complexes. In addition, lung permeability in metalloela stase-deficient mice was similar to 50% of that of injured parent strain an imals with normal levels of metalloelastase and this was correlated with hi stological evidence of less lung injury in the metalloelastase-deficient an imals. Collectively, the data suggest that metalloelastase is necessary for the full development of acute alveolitis in this model of lung injury. Fur ther, the data suggest that reduced injury in metalloelastase-deficient mic e is due in part to decreased neutrophil influx into the alveolar space.