Cytotoxicity and Wound Healing Evidence for the Role of Elastase in ARDS in Humans Animal Models of Lung Injury and Leukocyte Elastase Studies of Protease Inhibitors and Experimental Lung Injury Studies with Elastase Knockout Mice Studies of Elastase Inhibitors in Human Lung Injury in Sepsis Conclusions and Unanswered Questions A balance between injury and benefit: a modulator of the inflammatory response?

The syndrome of acute lung injury, known in its most severe form as the acute respiratory distress syndrome (ARDS), is characterized by increased alveolocapillary membrane permeability and subsequent pulmonary edema. Acute lung injury can be initiated by any one of an extensive and heterogeneous list of pulmonary or systemic insults, the most frequent of which is sepsis (1). What these inciting factors have in common is the ability to initiate activation of an acute inflammatory response that apparently spirals out of control, leading to pulmonary parenchymal injury. Neutrophilic polymorphonuclear leukocytes (neutrophils, PMN), which normally pass through the lung relatively unimpeded, are sequestered and activated in the pulmonary microvasculature during the genesis of an inflammatory response. The activation of neutrophils leads to the release of multiple microbicidal products, including reactive oxygen species, cationic peptides, eicosanoids, and proteolytic enzymes that normally serve in host defense