3.4.21.37: leukocyte elastase
This is an abbreviated version!
For detailed information about leukocyte elastase, go to the full flat file.
Word Map on EC 3.4.21.37
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3.4.21.37
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pulmonary
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cathepsin
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airway
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pancreatic
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lavage
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myeloperoxidase
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hne
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emphysema
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fibrosis
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cystic
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bronchoalveolar
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granule
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elastin
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sputum
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bronchial
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thrombin
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chymotrypsin
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coagulation
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1-antitrypsin
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neutropenia
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interleukin-8
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1-proteinase
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degranulation
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c-reactive
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cardiopulmonary
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elastolytic
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antiprotease
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serpins
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mucus
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slpi
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alpha1-antitrypsin
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azurophilic
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aa
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neutrophil-derived
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elastases
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2-macroglobulin
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bronchiectasis
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fmlp
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elastase-induced
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netosis
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antineutrophil
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proteinase-3
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thrombin-antithrombin
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ulinastatin
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crevicular
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neutrophil-mediated
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ne-induced
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beta-thromboglobulin
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drug development
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wegener
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2-antiplasmin
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diagnostics
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medicine
- 3.4.21.37
- pulmonary
- cathepsin
- airway
- pancreatic
-
lavage
- myeloperoxidase
- hne
- emphysema
- fibrosis
-
cystic
-
bronchoalveolar
- granule
- elastin
- sputum
- bronchial
- thrombin
- chymotrypsin
- coagulation
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1-antitrypsin
- neutropenia
- interleukin-8
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1-proteinase
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degranulation
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c-reactive
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cardiopulmonary
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elastolytic
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antiprotease
- serpins
- mucus
- slpi
- alpha1-antitrypsin
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azurophilic
- aa
-
neutrophil-derived
- elastases
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2-macroglobulin
- bronchiectasis
- fmlp
-
elastase-induced
-
netosis
-
antineutrophil
- proteinase-3
-
thrombin-antithrombin
- ulinastatin
-
crevicular
-
neutrophil-mediated
-
ne-induced
-
beta-thromboglobulin
- drug development
-
wegener
-
2-antiplasmin
- diagnostics
- medicine
Reaction
Hydrolysis of proteins, including elastin. Preferential cleavage Val-/- > Ala-/- =
Synonyms
bone marrow serine protease, EC 3.4.21.11, EC 3.4.4.7, ELA2, Elane, elastase, elaszym, granulocyte elastase, H2A specific protease, H2Asp, HLE, HNE, leukocyte elastase, lysosomal elastase, N-elastase, NE, neutrophil elastase, neutrophil-elastase, neutrophil-released elastase, PMN elastase, PMN-elastase, PMNE, polymorphonuclear leukocyte elastase, polymorphonuclear neutrophil elastase, serine elastase
ECTree
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Natural Substrates Products
Natural Substrates Products on EC 3.4.21.37 - leukocyte elastase
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REACTION DIAGRAM
alpha1-PI + H2O
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important antiprotease of the lung, enzyme reduces the lungs primary protection against proteolysis
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annexin 1 + H2O
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annexin 1 is externalized and truncated upon adhesion of polymorphonuclear leukocytes to endothelial cells, annexin 1 participates in regulating leukocyte emigration into inflamed tissue through N-terminal peptides generated at inflammatory sites, overview
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BP180/type XVII collagen + H2O
peptide p561 + peptide p506
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neutrophil elastase degrades recombinant mouse BP180 within the immunodominant extracellular domain at amino acid positions 506 and 561
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corticosteroid-binding globulin + H2O
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cleavage by neutrophil elastase destroys ligand binding capacity and supposedly liberates cortisol at sites of inflammation. Enzyme activity on wild-type and mutant CBG serpin recombinantly produced by 293-EBNA cells, overview. CBG mutant G335V is more sensitive for elastase cleavage, while CBG mutant T342A is more resistant to elastase cleavage
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Factor VIIIa + H2O
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neutrophil elastase inactivates factor VIIIa. The enzyme proteolyses the heavy chain of factor VIIIa into two terminal products, A11-358 and A2375-708, by limited proteolysis at Val358, Val374, and Val708
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G-CSF receptor + H2O
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neutrophil elastase proteolytically cleaves the G-CSF receptor, G-CSFR, a transmembrane protein, in its extracellular region on neutrophils and blocks G-CSFR-mediated granulopoiesis in vitro, and growth of neutrophils and monocytes, CFU-GM, overview
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?
human SP-D protein + H2O
SP-D protein peptide fragments
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cleavage in the lungs of the cystic fibrosis human host, but not in helathy human hosts
cleavage product identification by N-terminal sequencing, overview
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?
IgA + H2O
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involved in the regulation of inflammation by a feedback mechanism, elastase treated IgA preparations are unable to induce oxidative burst of polymorphonuclear leukocytes
protein cleaved in the hinge region
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?
IgG + H2O
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involved in the regulation of inflammation by a feedback mechanism, elastase treated IgG preparations are unable to induce oxidative burst of polymorphonuclear leukocytes
protein cleaved in the hinge region
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?
interleukin-36 receptor antagonist + H2O
activated interleukin-36 receptor antagonist V2 + ?
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the enzyme cleaves 9 amino acids upstream of the A-X-D consensus of interleukin-36 receptor antagonist
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IpaB protein + H2O
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neutrophil elastase cleaves IpaB protein after alanine, valine, isoleucine, or threonine residues
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methoxysuccinyl-Ala-Ala-Pro-Val-4-nitroanilide + H2O
methoxysuccinyl-Ala-Ala-Pro-Val + 4-nitroanilide
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?
mucin + H2O
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proteolysis of mucin is suggested to be involved in cell damaging processes during chronic infection and inflammation of the respiratory tract
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oxytalan fibre + H2O
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the elastase degrades the interfibrillar substances in the periodontal ligament and exposed individual collagen fibrils but not the collagen fibers of the transverse sections of rat mandibular first molars
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procarboxypeptidase R + H2O
carboxypeptidase R + ?
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generation of activated carboxypeptidase R from procarboxypeptidase R by elastase from activated neutrophils at the site of inflammation should contribute to the suppression of excessive inflammation and any abnormality in this mechanism can induce serious hyper-inflammation such as seen in multiple organ failure
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protein C + H2O
small peptides
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the enzyme splits protein C in vitro and also in vivo degradation of protein C may take place
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?
proteinase-activated receptor 2 N-terminus + H2O
GPNSKGRSLIGRLDTPPPITGKGAPVEPGFSVDEFSAS + VLTGKLTTVFLP
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secretory leucoprotease inhibitor + H2O
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i.e. SLPI, SLPI is cleaved and inactivated by neutrophil elastase in cystic fibrosis lungs
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SLPI + H2O
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important antiprotease of the lung, enzyme reduces the lungs primary protection against proteolysis
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SP-D protein + H2O
SP-D protein peptide fragments
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no activity in healthy lungs, but in 50% of cystic fibrosis patient lungs
cleavage product identification by N-terminal sequencing, overview
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?
elafin + H2O
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elafin is cleaved by its cognate enzyme neutrophil elastase, neutrophil elastase-mediated cleavage of elafin abolishes the capacity of the inhibitor to cross-link to fibronectin by transglutamination, neutrophil elastase-mediated cleavages of elafin at Val5-Lys-6 and Val9-Ser10 peptide bonds only occur with 2x excess of neutrophil elastase, a partial cleavage of the inhibitor is identified at the scissile peptide bond Ala24-Met25
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged
protein cleaved at at least one location
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Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, involved in the etiology of emphysema, rheumatoid arthritis, psoriasis, and adult respiratory distress syndrome
protein cleaved at at least one location
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?
Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged
protein cleaved at at least one location
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?
Elastin + H2O
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697329, 697826, 698394, 717369, 717904, 718421, 731106, 731124, 731591, 731788, 731991, 732294, 732438, 732564, 732600, 732758, 732907, 754758
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Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells also might be damaged, involved in the onset of emphysema and rheumatoid arthritis
protein cleaved at at least one location
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?
Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged
protein cleaved at at least one location
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?
Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, enzyme is assumed to play a key role in the gradual decrease of lung function during cystic fibrosis
protein cleaved at at least one location
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?
Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, involved in the etiology of emphysema, rheumatoid arthritis, psoriasis, and adult respiratory distress syndrome
protein cleaved at at least one location
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?
Elastin + H2O
?
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, involved in the onset of emphysema, acute respiratory distress syndrome, and rheumatoid arthritis
protein cleaved at at least one location
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?
Elastin + H2O
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generation of soluble peptides by limited proteolysis, elastin-derived peptides play roles in cell migration, differentiation, proliferation, chemotaxis, tumor progression, and up-regulation of metalloproteinases, the sequence GXXPG is required within the enzyme to stimulate the cellular effects, overview
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Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, involved in the etiology of emphysema, rheumatoid arthritis, psoriasis, and adult respiratory distress syndrome
protein cleaved at at least one location
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?
Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged
protein cleaved at at least one location
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?
Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, could participate in neutrophil migration
protein cleaved at at least one location
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?
Elastin + H2O
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, involved in the etiology of emphysema, rheumatoid arthritis, psoriasis, and adult respiratory distress syndrome
protein cleaved at at least one location
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?
Elastin + H2O
?
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, involved in the onset of emphysema and rheumatoid arthritis
protein cleaved at at least one location
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?
Elastin + H2O
?
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involved in lung defense against bacterial infection, due to the ability of the enzyme to cleave cell surface proteins, body cells might also be damaged, involved in the etiology of emphysema, rheumatoid arthritis, psoriasis, and adult respiratory distress syndrome
protein cleaved at at least one location
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?
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catalyzes the inactivation of antithrombin by a specific and limited proteinolytic cleavage
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additional information
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elastase in contrast to human elastase, may play a minor role in mediating tissue damage and organ failure
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additional information
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the enzyme may contribute to the intracellular degradation of phagocytized material, its release from activated polymorphonuclear leukocytes into extracellular spaces. The enzyme has been implicated in the pathogenesis of various diseases and is thought to be responsible for tissue damage
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additional information
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proteolysis of connective tissue by enzymes such as PMN-elastase is a crucial step during inflammation and metastasis
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additional information
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imbalance between elastase and its endogenous inhibitors may result in several pathophysiological states such as chronic obstructive pulmonary disease, asthma, emphysema, cystic fibrosis and chronic inflammatory diseases
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additional information
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neutrophil elastase is a key component of the bodys inflammatory defenses, assisting the neutrophil in its migration to the site of inflammation and participating in the proteolytic degradation of invading microorganisms. In addition the enzyme is involved in tissue remodeling and wound healing. Under homeostatic conditions, the destructive effects of the enzyme are limited to the microenvironment immediately surrounding the neutrophil by endogenous proteinase inhibitors such as alpha1-proteinase inhibitor. As a consequence of chronic inflammation, however, the balance between the enzyme and alpha1-antitrypsin can be shifted in favor of the enzyme, resulting in uncontrolled tissue destruction. The enzyme has been implicated in the promotion or exacerbation of a number of diseases including pancreatitis acute respiratory distress syndrome, rheumatoid arthritis, atherosclerosis, pulmonary emphysema and cystic fibrosis
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additional information
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the enzyme may be involved in a number of important disease states. Including the pulmonary emphysema associated with a hereditary deficiency of alpha1-proteinase inhibitor
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additional information
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leukocyte elastase induces keratinocyte proliferation by epidermal growth factor receptor activation
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additional information
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neutrophil elastase induces MUC5AC mucin production in human airway epithelial cells via a cascade involving protein kinase C, reactive oxygen species, and TNF-alpha-converting enzyme
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additional information
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release of leukocyte elastase and cathepsin G from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin play an important role in the down-regulation of acute inflammation
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additional information
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a massive release of PMN-elastase from neutrophils occurs during surgical procedures, effects on the enzyme of cholecystectomy via laparoscopic or open surgical operation of patients with gallbladder cholethiasis, overview
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additional information
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inflammatory lung secretions inhibit dendritic cell maturation and function via neutrophil elastase, neutrophil elastase downregulated the expression of CD40, CD80, and CD86, but of not major histocompatibility complex II, on dendritic cells and inhibited LPS-induced dendritic cell maturation, and the the antigen-presenting ability of muring dendritic cells, overview
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additional information
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neutrophil elastase converts human immature dendritic cells into transforming growth factor-beta1-secreting cells and reduces allostimulatory ability, elastase induces IkappaBalpha degradation in dendritic cells, overview
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additional information
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neutrophil elastase, a component of the innate host defense system, is bactericidal for Gram-negative bacteria and degrades bacterial virulence factors, resistance of Pseudomonas aeruginosa to the bactericidal effect of neutrophil elastase, as well as this organisms ability to sense this enzymes presence and downregulate the synthesis of a pathogen-associated molecular pattern, may be the key factors in allowing Pseudomonas aeruginosa to colonize the lungs, overview
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additional information
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the enzyme digests microbes after phagocytosis in polymorphonuclear neutrophil primary granules, which fuse with neutrophil phagolysosomes, and also acts extracellularly at sites of inflammation, overview, mutations in the human neutrophil elastase gene cause cyclic and congenital neutropenia leading to an immunodeficiency characterized by decreased or oscillating levels of neutrophils in the blood
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additional information
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the enzyme digests microbes after phagocytosis in polymorphonuclear neutrophil primary granules, which fuse with neutrophil phagolysosomes, and also acts extracellularly at sites of inflammation, overview, mutations in the human neutrophil elastase gene cause cyclic and congenital neutropenia leading to an immunodeficiency characterized by decreased or oscillating levels of neutrophils in the blood
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additional information
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human neutrophil elastase induces interleukin-8 release from HUVEC cells
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additional information
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neutrophil elastase possesses potent microbicidal activity, and is speculated to assist with phagocytosis of pathogens by activated neutrophils, moreover, neutrophil elastase can indirectly help the host eradication of pathogens by upregulating the expression of potent antiprotease/antimicrobial agents such as elafin, secretory leukocyte protease inhibitor, and human beta defensin-2
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additional information
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neutrophil elastase reduces secretion of secretory leukoproteinase inhibitor by lung epithelial cells
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additional information
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leukocyte elastase induces binding activity of NF-kappaB to lung epithelial cells, and induces phosphorylation of p53 on Ser46 and alters its localization. And leukocyte elastase induces expression of PUMA, a p53-upregulated modulator of apoptosis
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additional information
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neutrophil elastase does not cleave the N-terminal domains and does not disarm either PAR-1 or PAR-2
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additional information
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neutrophil elastase induces NF-kappaB activation by p65 in airway smooth muscle, which leads to induction of TGF-beta1. Neutrophil elastase suppresses NF-kappaB response gene IL-8/CXCL8 release and mRNA expression in airway smooth muscle cells at the transcription level mediated by induction of NF-kappaB repressing factor, NRF. In A549 and Beas-2B cells, neutrophil elastase only stimulates NF-kappaB activation by p65 and IL-8/CXCL8 induction, but not NRF, overview
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additional information
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neutrophil elastase interacts with phosphonoformate immunoassociated protein 5, i.e. PFAAP5 or N4BP2L2, with potential participation in a feedback circuit in which neutrophil elastase regulates its own transcription
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additional information
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histone H3 is not degraded by neutrophil elastase
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additional information
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the enzyme prefers L-Val in the P1 position but also cleaves substrates with L-Ile relatively efficiently and does not cleave after aromatic amino acids
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additional information
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neutrophil elastase influences the proliferation and differentiation of primary early myeloid cells expressing low levels of PML-retioic acid receptor alpha
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additional information
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involvement of neutrophil elastase in leukotriene B4-induced neutrophil transmigration in vivo, specific NE inhibitor suppresses neutrophil migration through IL-1beta-stimulated cremasteric venules at the level of the basement membrane
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additional information
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the enzyme digests microbes after phagocytosis in polymorphonuclear neutrophils, as well as extracellularly, but causes tissue damage and inflammation in the latter case, serine protease inhibitor 6-deficient Spi6 KO mice have increased neutrophil immunity to Pseudomonas aeruginosa, enzyme inhibitor Spi6 protects the cells from self-inflicted damage, the enzyme protects against Pseudomonas aeruginosa infection, overview
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additional information
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neutrophil elastase is required for maximal intracellular killing of Pseudomonas aeruginosa by neutrophils
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additional information
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the enzyme digests microbes after phagocytosis in polymorphonuclear neutrophils, as well as extracellularly, but causes tissue damage and inflammation in the latter case, serine protease inhibitor 6-deficient Spi6 KO mice have increased neutrophil immunity to Pseudomonas aeruginosa, enzyme inhibitor Spi6 protects the cells from self-inflicted damage, the enzyme protects against Pseudomonas aeruginosa infection, overview
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additional information
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neutrophils and the elastase thereof play a role in the progression of gut barrier dysfunction during acut alveolar hypoxia, inhibition of neutrophil elastase attenuates gut mucosal injury evoked by acute alveolar hypoxia in rabbits, overview
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additional information
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elastase in contrast to human elastase, may play a minor role in mediating tissue damage and organ failure
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