Neutrophil elastase

Gene

In humans, neutrophil elastase is encoded by the ELANE gene, which resides on chromosome 11.

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. 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. 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.

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. In 2019, a study confirmed that ELANE deletion does not cause neutropenia.

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). Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin, which belongs to the Serpin family of proteins.

References

References

1. (August 2000). "Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase". Science.
2. (June 2014). "Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins". J. Immunol..
3. (October 1988). "Structure of the human neutrophil elastase gene". J. Biol. Chem..
4. (May 2002). "Neutrophil elastase targets virulence factors of enterobacteria". Nature.
5. (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports.
6. "Entrez Gene: ELA2 elastase 2, neutrophil".
7. (January 2009). "The many causes of severe congenital neutropenia". N. Engl. J. Med..
8. (August 2019). "ELANE whole gene deletion mutation". Blood Advances.
9. (December 2010). "Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases". Pharmacol. Rev..
10. (August 1982). "Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase". J. Biol. Chem..
11. (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem..