関: neutrophil elastase

WordNet

blood cells that engulf and digest bacteria and fungi; an important part of the bodys defense system (同)leucocyte, white_blood_cell, white_cell, white blood corpuscle, white_corpuscle, WBC
a pancreatic enzyme that catalyzes the hydrolysis of elastin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/09 10:49:22」(JST)

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Neutrophil elastase (EC 3.4.21.37, 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.^[1] It also localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.^[2]

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.^[2]

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 ELANE gene, which resides on chromosome 19.^[3]

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.^[4] 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.^[5]

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 severe congenital neutropenia, which is a failure of neutrophils to mature.^[6]

Interactions

Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin.^[7]^[8]

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.
^ ^a ^b Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M et al. (June 2014). "Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins". J. Immunol. 192 (11): 5390–7. doi:10.4049/jimmunol.1303296. PMC 4041364. PMID 24771851.
^ Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD et al. (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. PMC 4162527. PMID 19118300.
^ 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. PMID 6980881.
^ Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. 262 (13): 6055–9. 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)

UpToDate Contents

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1. 先天性好中球減少症 congenital neutropenia
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English Journal

Repurposing a leukocyte elastase inhibitor for neuropathic pain.

Weyer AD1, Stucky CL1.
Nature medicine.Nat Med.2015 May 7;21(5):429-30. doi: 10.1038/nm.3861.
PMID 25951529

Protease-antiprotease imbalances differ between Cystic Fibrosis patients' upper and lower airway secretions.

Hentschel J1, Fischer N2, Janhsen WK2, Markert UR3, Lehmann T4, Sonnemann J5, Böer K6, Pfister W7, Hipler UC8, Mainz JG2.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.J Cyst Fibros.2015 May;14(3):324-33. doi: 10.1016/j.jcf.2014.09.003. Epub 2014 Oct 5.
BACKGROUND: Balanced levels of proteases and anti-proteases are essential in host defense systems. In CF patients' lungs, elevated protease/anti-protease-ratios contribute to damage of airway tissue and premature death with the inherited disease. Little is known about upper airway protease equilibri
PMID 25286826

The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase.

Vicuña L1, Strochlic DE2, Latremoliere A3, Bali KK1, Simonetti M1, Husainie D1, Prokosch S4, Riva P5, Griffin RS6, Njoo C1, Gehrig S7, Mall MA7, Arnold B4, Devor M8, Woolf CJ3, Liberles SD2, Costigan M9, Kuner R1.
Nature medicine.Nat Med.2015 May;21(5):518-23. doi: 10.1038/nm.3852. Epub 2015 Apr 27.
Neuropathic pain is a major, intractable clinical problem and its pathophysiology is not well understood. Although recent gene expression profiling studies have enabled the identification of novel targets for pain therapy, classical study designs provide unclear results owing to the differential exp
PMID 25915831

Japanese Journal

血栓溶解機構とその制御 (特集血栓・塞栓症 : 治療・予防の最新動向) -- (基礎研究の進歩)

日本臨床 72(7), 1218-1223, 2014-07
NAID 40020130981

分子マーカーの現在(第4回)Fibrinogen and fibrin degradation products (FDP), D-dimer, Cross-linked fibrin degradation products by leukocyte elastase (e-XDP)

Thrombosis medicine 2(2), 159-165, 2012-06
NAID 40019361668

Toxicoproteomics of the mixture of Di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) in male sprague-dawley rats

日本毒性学会学術年会 39.2(0), AP-142, 2012
NAID 130005009078

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Elastase, neutrophil expressed
	PDB rendering based on 1b0f.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1B0F, 1H1B, 1HNE, 1PPF, 1PPG, 2RG3, 2Z7F, 3Q76, 3Q77
Identifiers
Symbols	ELANE ; ELA2; GE; HLE; HNE; NE; PMN-E; SCN1
External IDs	OMIM: 130130 MGI: 2679229 HomoloGene: 20455 IUPHAR: 2358 ChEMBL: 248 GeneCards: ELANE Gene
EC number	3.4.21.37
Gene ontology
Molecular function	• RNA polymerase II transcription corepressor activity; • protease binding; • endopeptidase activity; • serine-type endopeptidase activity; • protein binding; • heparin binding; • peptidase activity; • cytokine binding;
Cellular component	• extracellular region; • cytoplasm; • cell surface; • transcriptional repressor complex; • secretory granule; • extracellular vesicular exosome;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • response to yeast; • acute inflammatory response to antigenic stimulus; • proteolysis; • cellular calcium ion homeostasis; • phagocytosis; • response to UV; • extracellular matrix disassembly; • protein catabolic process; • extracellular matrix organization; • collagen catabolic process; • response to lipopolysaccharide; • defense response to bacterium; • positive regulation of MAP kinase activity; • negative regulation of growth of symbiont in host; • negative regulation of chemokine biosynthetic process; • negative regulation of interleukin-8 biosynthetic process; • positive regulation of interleukin-8 biosynthetic process; • positive regulation of smooth muscle cell proliferation; • negative regulation of inflammatory response; • positive regulation of immune response; • leukocyte migration; • negative regulation of chemotaxis; • neutrophil mediated killing of fungus;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

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英
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同: leukocyte elastase

英: [[]]
同: leukocyte elastase

[pmid10947984-1] 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.

[Thomas-2] Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M et al. (June 2014). "Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins". J. Immunol. 192 (11): 5390–7. doi:10.4049/jimmunol.1303296. PMC 4041364. PMID 24771851.

[pmid2902087-3] Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD et al. (October 1988). "Structure of the human neutrophil elastase gene". J. Biol. Chem. 263 (29): 14739–47. PMID 2902087.

[pmid12018205-4] 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.

[5] "Entrez Gene: ELA2 elastase 2, neutrophil".

[pmid19118300-6] 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. PMC 4162527. PMID 19118300.

[pmid6980881-7] 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. PMID 6980881.

[pmid2437112-8] Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. 262 (13): 6055–9. PMID 2437112.

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案内

leukocyte elastase