• cytoplasm • transcriptional repressor complex • secretory granule • extracellular region • cell surface • extracellular exosome • extracellular space • azurophil granule lumen • specific granule lumen
Biological process
• response to yeast • positive regulation of MAP kinase activity • negative regulation of growth of symbiont in host • negative regulation of chemotaxis • cellular calcium ion homeostasis • extracellular matrix disassembly • acute inflammatory response to antigenic stimulus • negative regulation of transcription from RNA polymerase II promoter • negative regulation of interleukin-8 biosynthetic process • defense response to fungus • proteolysis • response to lipopolysaccharide • positive regulation of immune response • protein catabolic process • defense response to bacterium • phagocytosis • neutrophil mediated killing of fungus • negative regulation of chemokine biosynthetic process • positive regulation of interleukin-8 biosynthetic process • negative regulation of inflammatory response • response to UV • leukocyte migration • positive regulation of smooth muscle cell proliferation • leukocyte migration involved in inflammatory response • positive regulation of leukocyte tethering or rolling • antimicrobial humoral response • neutrophil degranulation
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
1991
50701
Ensembl
ENSG00000277571 ENSG00000197561
ENSMUSG00000020125
UniProt
P08246
Q3UP87
RefSeq (mRNA)
NM_001972
NM_015779
RefSeq (protein)
NP_001963
NP_056594
Location (UCSC)
Chr 19: 0.85 – 0.86 Mb
Chr 10: 79.89 – 79.89 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
Neutrophil elastase (EC 3.4.21.37, 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. Secreted by neutrophils and macrophages during inflammation, it 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]
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.
Contents
1Gene
2Function
3Clinical significance
4Inhibitors
5See also
6References
7Further reading
8External links
Gene
In humans, neutrophil elastase is encoded by the ELANE gene, which resides on chromosome 19.[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 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.[9]
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.[10]
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).[11] Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin, which belongs to the Serpin family of proteins.[12][13]
^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.
^ abThomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M, Lieberman J (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, 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. PMC 4162527. PMID 19118300.
^Korkmaz B, Horwitz MS, Jenne DE, Gauthier F (December 2010). "Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases". Pharmacol. Rev. 4 (62): 726–59. doi:10.1124/pr.110.002733. PMC 2993259. PMID 21079042.
^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.
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. PMID 11846296.
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. 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, Li FQ, Person RE (2004). "Hereditary neutropenia: dogs explain human neutrophil elastase mutations". Trends Mol Med. 10 (4): 163–70. doi:10.1016/j.molmed.2004.02.002. PMID 15059607.
External links
GeneReviews/NCBI/NIH/UW entry on ELANE-Related Neutropenias
Neutrophil+Elastase at the US National Library of Medicine Medical Subject Headings (MeSH)
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PDB gallery
1b0f: CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146
1h1b: CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE COMPLEXED WITH AN INHIBITOR (GW475151)
1hne: STRUCTURE OF HUMAN NEUTROPHIL ELASTASE IN COMPLEX WITH A PEPTIDE CHLOROMETHYL KETONE INHIBITOR AT 1.84-ANGSTROMS RESOLUTION
1ppf: X-RAY CRYSTAL STRUCTURE OF THE COMPLEX OF HUMAN LEUKOCYTE ELASTASE (PMN ELASTASE) AND THE THIRD DOMAIN OF THE TURKEY OVOMUCOID INHIBITOR
1ppg: THE REFINED 2.3 ANGSTROMS CRYSTAL STRUCTURE OF HUMAN LEUKOCYTE ELASTASE IN A COMPLEX WITH A VALINE CHLOROMETHYL KETONE INHIBITOR
12.7 cm/40 Type 89 naval gun Type 89 gun mounted on Chitose Type Naval gun anti-aircraft gun Place of origin Japan Service history In service 1932–45 Used by Imperial Japanese Navy Wars World War II Production history Designed 1928–32 Produced 1932–45 No. built ~1500 Variants Type 88 Specifications Mass 3,100 kilograms (6,834 lb) Barrel length 5,080 millimeters (16 ft 8 in) (bore length) Shell Fixed Shell weight 20.9–23.45 kilograms (46.1–51.7 lb) Caliber 12.7-centimeter (5.0 in) Breech horizontal breech block Elevation -8° to +90° [1] Rate of fire 8-14 rounds per minute Muzzle velocity 720–725 meters per second (2,360–2,380 ft/s) Maximum firing range 9,440 meters (30,970 ft) at 90° (AA ceiling) 14,800 meters (48,600 ft) at 45° The 12.7 cm/40 Type 89 naval gun was a Japanese anti-aircraft (AA) gun introduced before World War II. It was the Imperial Japanese Navy's standard heavy AA
For other uses, see Shark (disambiguation). Sharks Temporal range: Ludfordian-Present, 425–0 Ma PreЄ Є O S D C P T J K Pg N [1] Clockwise from top left: spiny dogfish, Japanese sawshark, whale shark, great white shark, horn shark, frilled shark, scalloped hammerhead and Australian angelshark representing the orders Squaliformes, Pristiophoriformes, Orectolobiformes, Lamniformes, Heterodontiformes, Hexanchiformes, Carcharhiniformes and Squatiniformes respectively. Scientific classification Kingdom: Animalia Phylum: Chordata Class: Chondrichthyes Subclass: Elasmobranchii Infraclass: Euselachii Superorder: Selachimorpha Orders Carcharhiniformes Heterodontiformes Hexanchiformes Lamniformes Orectolobiformes Pristiophoriformes Squaliformes Squatiniformes † Cladoselachiformes † Hybodontiformes † Symmoriida † Xenacanthida (Xenacantiformes) † Elegestolepis † = extinct Synonyms Pleurotremata Sharks
Wiciokrzew, suchodrzew Morfologia (wiciokrzew pospolity) Systematyka [1] Domena eukarionty Królestwo rośliny Klad rośliny naczyniowe Klad rośliny nasienne Klasa okrytonasienne Klad astrowe Rząd szczeciowce Rodzina przewiertniowate Rodzaj wiciokrzew Nazwa systematyczna Lonicera L. Sp. Pl. 173. 1 Mai 1753 Typ nomenklatoryczny Lonicera caprifolium L. [2] Multimedia w Wikimedia Commons Hasło w Wikisłowniku Kwiaty suchodrzewu pospolitego Owoce suchodrzewu pospolitego Kwiaty wiciokrzewu pomorskiego Kwiaty wiciokrzewu przewiercienia Wiciokrzew , suchodrzew ( Lonicera L.) – rodzaj roślin wieloletnich należący do rodziny przewiertniowatych ( Caprifoliaceae ). Rośliny zielne i pnące nazywane są wiciokrzewami, natomiast krzewy i niewielkie drzewa – suchodrzewami. Rodzaj liczy około 180 gatunków szeroko rozprzestrzenionych na całej półkuli północnej [3] [4]
