Neutrophil elastase (EC126.96.36.199, leukocyte elastase, ELANE, ELA2, elastase 2, neutrophil, elaszym, serine elastase) is a serine proteinase in the same family as chymotrypsin and has broad substrate specificity. Secreted by neutrophils and macrophages during inflammation, it destroys bacteria and host tissue. It also localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.
As with other serine proteinases it contains a charge relay system composed of the catalytic triad of histidine, aspartate, and serine residues that are dispersed throughout the primary sequence of the polypeptide but that are brought together in the three dimensional conformation of the folded protein. The gene encoding neutrophil elastase, ELA2, consists of five exons. Neutrophil elastase is closely related to other cytotoxic immune serine proteases, such as the granzymes and cathepsin G. It is more distantly related to the digestive CELA1.
Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes that encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Neutrophil elastase hydrolyzes proteins within specialized neutrophil lysosomes, called azurophil granules, as well as proteins of the extracellular matrix following the protein's release from activated neutrophils. Neutrophil elastase may play a role in degenerative and inflammatory diseases by its proteolysis of collagen-IV and elastin of the extracellular matrix. This protein degrades the outer membrane protein A (OmpA) of E. coli as well as the virulence factors of such bacteria as Shigella, Salmonella and Yersinia. Mutations in this gene are associated with cyclic neutropenia and severe congenital neutropenia (SCN). This gene is clustered with other serine protease gene family members, azurocidin 1 and proteinase 3 genes, at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation.
Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause emphysema or emphysematous changes. This involves breakdown of the lung structure and increased airspaces. Mutations of the ELANE gene cause severe congenital neutropenia, which is a failure of neutrophils to mature.
^Brower MS, Harpel PC (August 1982). "Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase". J. Biol. Chem.257 (16): 9849–54. PMID6980881.
^Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem.262 (13): 6055–9. PMID2437112.
Dale DC, Liles WC, Garwicz D, Aprikyan AG (2001). "Clinical implications of mutations of neutrophil elastase in congenital and cyclic neutropenia". J. Pediatr. Hematol. Oncol.23 (4): 208–10. doi:10.1097/00043426-200105000-00005. PMID11846296.
Horwitz M, Benson KF, Duan Z, Person RE, Wechsler J, Williams K et al. (2003). "Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis". Curr. Opin. Hematol.10 (1): 49–54. doi:10.1097/00062752-200301000-00008. PMID12483111.