Neutrophil elastase

Neutrophil elastase (, leukocyte elastase, ELANE, ELA2, elastase 2, neutrophil, elaszym, serine elastase) is a serine is_associated_with::proteinase in the same family as is_associated_with::chymotrypsin and has broad substrate specificity. Secreted by neutrophils and macrophages during inflammation, it destroys bacteria and host tissue. It also localizes to is_associated_with::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 is_associated_with::histidine, is_associated_with::aspartate, and is_associated_with::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 is_associated_with::exons. Neutrophil elastase is closely related to other cytotoxic immune serine proteases, such as the is_associated_with::granzymes and is_associated_with::cathepsin G. It is more distantly related to the digestive CELA1.

The neutrophil form of elastase is 218 is_associated_with::amino acids long, with two is_associated_with::asparagine-linked is_associated_with::carbohydrate chains (see is_associated_with::glycosylation). It is present in is_associated_with::azurophil granules in the neutrophil is_associated_with::cytoplasm. There appear to be two forms of neutrophil elastase, termed IIa and IIb.

Gene
In humans, neutrophil elastase is encoded by the ELANE is_associated_with::gene, which resides on chromosome 19.

Function
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 is_associated_with::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 is_associated_with::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 is_associated_with::azurophil granules during neutrophil differentiation.

Clinical significance
Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause is_associated_with::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.

Interactions
Neutrophil elastase has been shown to interact with is_associated_with::Alpha 2-antiplasmin.