ABSTRACT
Human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), is a serine protease that is responsible for the abnormal turnover of connective-tissue proteins associated with the development of pulmonary emphy sema, rheumatoid arthritis, and several inflammatory diseases such as acute respiratory distress syndrome (ARDS) and septicemia (1). HLE is found in the azurophilic granules of polymorphonuclear leukocytes (neutrophils) and has im portant roles in phagocytosis. Extracellular HLE released from neutrophils is controlled by plasma protease inhibitors, primarily the serpin alpha 1-proteinase inhibitor (alPI). Conditions leading to a decrease in active a lP I concentration, such as a genetic defect or oxidative destruction of a lP I by cigarette smoking, can result in a protease-protease inhibitor imbalance, which is believed to be respon sible for pulmonary emphysema. One approach to the treatment of emphysema is the use of low-molecular-weight elastase inhibitors. Synthetic inhibitors have several advantages over natural protein protease inhibitors: they can be produced
Abbreviations are defined following the text.
