Neutrophil elastase
Neutrophil elastase (EC 3.4.21.37, leukocyte elastase, 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.[1]
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 dimension conformation of the folded protein. The gene encoding neutrophil elastase, ELA2, consists of five exons. It is one of the two human forms of elastase.
The neutrophil form of elastase (EC 3.4.21.37) is 218 amino acids long, with two asparagine-linked carbohydrate chains (see glycosylation). It is present in azurophil granules in the neutrophil cytoplasm. There appear to be two forms of neutrophil elastase, termed IIa and IIb.
Gene
In humans, neutrophil elastase is encoded by the ELA2 gene, which resides on chromosome 19.[2]
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. Elastase 2 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. Elastase 2 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.[3] 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.[4]
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 ELA2 gene cause severe congenital neutropenia, which is a failure of neutrophils to mature.[5]
See also
Interactions
Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin.[6][7]
References
- ↑ Belaaouaj A, Kim KS, Shapiro SD (August 2000). "Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase". Science 289 (5482): 1185–8. doi:10.1126/science.289.5482.1185. PMID 10947984.
- ↑ Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD, Whang-Peng J, Knutsen T, Crystal RG (October 1988). "Structure of the human neutrophil elastase gene". J. Biol. Chem. 263 (29): 14739–47. PMID 2902087.
- ↑ Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A (May 2002). "Neutrophil elastase targets virulence factors of enterobacteria". Nature 417 (6884): 91–4. doi:10.1038/417091a. PMID 12018205.
- ↑ "Entrez Gene: ELA2 elastase 2, neutrophil".
- ↑ Dale DC, Link DC (January 2009). "The many causes of severe congenital neutropenia". N. Engl. J. Med. 360 (1): 3–5. doi:10.1056/NEJMp0806821. PMID 19118300.
- ↑ Brower, M S; Harpel P C (August 1982). "Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase". J. Biol. Chem. (UNITED STATES) 257 (16): 9849–54. ISSN 0021-9258. PMID 6980881.
- ↑ Shieh, B H; Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. (UNITED STATES) 262 (13): 6055–9. ISSN 0021-9258. PMID 2437112.
External links
- GeneReviews/NCBI/NIH/UW entry on ELANE-Related Neutropenias
- Neutrophil Elastase at the US National Library of Medicine Medical Subject Headings (MeSH)
Further reading
- Dale DC, Liles WC, Garwicz D, Aprikyan AG (2002). "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. PMID 11846296.
- Horwitz M, Benson KF, Duan Z, 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. PMID 12483111.
- Ancliff PJ, Gale RE, Linch DC (2003). "Neutrophil elastase mutations in congenital neutropenia.". Hematology 8 (3): 165–71. doi:10.1080/1024533031000107497. PMID 12745650.
- Horwitz M, Benson KF, Duan Z, et al. (2004). "Hereditary neutropenia: dogs explain human neutrophil elastase mutations.". Trends in molecular medicine 10 (4): 163–70. doi:10.1016/j.molmed.2004.02.002. PMID 15059607.
| ||||||||||||||||
| ||||||||||||||||||||||||||