Neutrophil elastase (
EC3.4.21.37, leukocyte elastase, ELANE, ELA2, elastase 2, neutrophil, elaszym, serine elastase, subtype human leukocyte elastase (HLE)) is a serine
proteinase in the same family as
chymotrypsin and has broad substrate specificity. Neutrophil
elastase is secreted by
neutrophils during inflammation, and destroys
bacteria and host tissue.[5] It also localizes to
neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.[6]
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.[6]
In humans, neutrophil elastase is encoded by the ELANEgene, which resides on chromosome 11.[7]
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
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.[8] Mutations in this gene are associated with
cyclic neutropenia (CyN) and
severe congenital neutropenia (SCN). At least 95 disease-causing mutations in this gene have been discovered.[9] 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.[10]
Clinical significance
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
cyclic and
severe congenital
neutropenia, which is a failure of neutrophils to mature.[11] In 2019 study was confirmed that ELANE deletion does not cause neutropenia.[12]
Inhibitors
In order to minimize damage to tissues, there are few inhibitors of neutrophil elastase. One group of inhibitors are the
Serpins (Serine Protease Inhibitors).[13] Neutrophil elastase has been shown to
interact with
Alpha 2-antiplasmin, which belongs to the Serpin family of proteins.[14][15]
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, Albani D, Li FQ (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.
S2CID22277675.