[Structure and expression of the human neutrophil elastase gene--regulatory mechanism and its relevance to the respiratory diseases].
Human neutrophil elastase is a 29 kDa, 220-residue single chain glycoprotein which functions as a powerful serine protease. Because NE is capable of destroying a broad range of substrates including cross-linked elastin and the major forms of collagen as well as the cell walls of gram-negative bacilli, it possesses the two-edged sword property that is required for normal tissue turnover and host defense, yet potentially harmful in its ability to destroy normal tissues simultaneously. In this regard, NE plays a central role in the pathogenesis of pulmonary emphysema by destroying the alveolar walls of the lung in the conditions that antiproteases in the lung such as alpha 1-antitrypsin (alpha 1-AT) are inactivated-e.g., cigarette smoking, or alpha 1-AT deficiency caused by mutations of the alpha 1-AT gene-resulting in excess burden of NE in the lung. The gene encoding the NE protein has 5 exons and is located at chromosome 19p13.3. Expression of the NE gene is tightly controlled mainly at the transcriptional level, and limited to the early stage of myeloid cell differentiation in bone marrow cells, mostly in promyelocytes. The knowledge on the modulation of lineage- and differentiation-specific NE gene expression could offer the possible therapeutic strategy to the diseases such as pulmonary emphysema.
Yoshimura
K
K
Department of Gene Therapy, Jikei University School of Medicine.
Tanabe
O
O
D000595:Amino Acid Sequence; D001483:Base Sequence; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology*; D012140:Respiratory Tract Diseases / Q000201:enzymology
D019272:Leukocyte Elastase