ABSTRACT
Human neutrophil elastase (NE; EC 3.4.21.37) is a 29 kDa, 220-residue single chain glycoprotein that functions as a powerful serine protease. It is stored in the azurophilic (primary) granules of mature neutrophils and released when the neutrophil is activated or disintegrates (1-5). NE is capable of destroying a broad range of substrates, including cross-linked elastin, the major forms of collagen, the protein components of proteoglycans, fibronectin, laminin, components of the complement, coagulation cascades, and the cell walls of gram-negative bacilli such as Escherichia coli (1-5). In this regard, NE is considered a two-edged sword: it is required for normal tissue turnover and host defense yet is potentially harmful in its ability to destroy normal tissues simultaneously. For example, NE plays a central role in the pathogenesis of pulmonary emphysema by destroying the alveolar walls of the lung (6). Although natural substances with antiprotease activity in the lung, such as alpha 1 -antitrypsin (a l AT) or secretory leukoprotease inhibitor, could protect the lung from NE in the normal human body, the condi tions in which the normal alAT molecule is inactivated-e.g., cigarette smoking or alAT deficiency caused by mutations of the alA T gene-would result in excess burden of NE in the lung, causing pulmonary emphysema (6). Because of
its essential role in health and disease, it is important to understand the structure and expression of the gene that codes for the NE protein. Furthermore, elucidation of the mechanism that regulates expression of the NE gene in bone marrow cell differentiation is also crucial to develop the therapeutic strategy for such diseases as pulmonary emphysema.
