The role of neutrophil elastase in acute lung injury.
Beside its physiological function as a powerful host defense, neutrophil elastase is also known as one of the most destructive enzymes in the body. Current notion holds that neutrophil elastase is able to escape from regulation by multiple protease inhibitors at inflammatory sites. Once unregulated, this enzyme disturbs the function of the lung permeability barrier and induces the release of pro-inflammatory cytokines. These actions then cause symptoms that are typical in the pathophysiology of acute lung injury. In this article, we review recent progress in the understanding of the physiological activity of neutrophil elastase and its role in acute lung injury. Evidence in this review that supports the involvement of neutrophil elastase in the pathophysiology of acute lung injury includes: (1) neutrophil elastase levels are increased in both clinical and animal models of acute lung injury; (2) topical or systemic administration of neutrophil elastase produces typical symptoms of acute lung injury both in vitro and in vivo; and (3) inhibition of increased neutrophil elastase activity reduces symptoms of acute lung injury in animal models. A greater understanding of the role of this enzyme in the pathophysiology of acute lung injury will lead to better treatments for this complicated disease.
Kawabata
Kazuhito
K
Minase Research Institute, Ono Pharmaceutical Co, Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. k.kawabata@ono.co.jp
Hagio
Tetsuya
T
Matsuoka
Shozo
S
D000818:Animals; D006801:Humans; D019272:Leukocyte Elastase / Q000009:adverse effects / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D011480:Protease Inhibitors / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000503:physiopathology
D011480:Protease Inhibitors; D019272:Leukocyte Elastase