Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-1-protease inhibitor is susceptible to oxidative impairment by the neutrophil myeloperoxidase (MPO) system. The purpose of this study was to assess the effect of the MPO oxidant system on elastase-induced emphysema in the hamster. Intratracheal instillation of 200 micrograms of human neutrophil elastase (HNE) induced a significant secretory cell metaplasia (SCM) and airspace enlargement [23% increase in mean linear intercept (MLI) as compared with control values]. Instillation of MPO system components [0.6 international units (U) of MPO, 5.5 U of glucose oxidase and glucose (0.02 M)] along with 200 micrograms HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 micrograms of porcine pancreatic elastase (PPE) to induce emphysema. PPE produced a significant 45% increase in MLI, but the MPO system combined with PPE failed to enhance the emphysema induced by PPE alone. The MPO system alone had no measurable effect on airspace size or SCM. In vitro studies showed that PPE was partially inactivated by the MPO system; a 56% loss of elastolytic activity occurred during a 6-min incubation of PPE with the MPO system. This may explain why the MPO system did not exacerbate PPE-induced injury, but it does not explain the lack of enhancement for HNE. A 6-minute incubation of HNE with the MPO system resulted in a nonsignificant 10% decrease of elastolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidants from neutrophil myeloperoxidase do not enhance elastase-induced emphysema in the hamster. 821 Jul 17

Several studies have shown increased plasma concentrations of neutrophil elastase in complex with alpha 1-protease inhibitor and/or lactoferrin in inflammatory conditions, and serial measurements have been advocated in order to follow disease activity. However, data on the magnitude of the within-subject variation are necessary for evaluation of the significance of changes in results obtained on analysis of serial samples. Within-subject variation of elastase/alpha 1-protease inhibitor complexes and lactoferrin over a short time was studied in six young men who had blood samples drawn every 4 h over 2 days. Within-subject variation over a longer time was investigated in 12 healthy adults, 6 females and 6 males, who had blood samples drawn in the morning once a week for 10 weeks. From five of the females and five of the males, blood samples were also drawn every morning on 5 consecutive days during 1 week. Within-subject variations over hours, days, and weeks were estimated as 0.050, 0.124, and 0.148 for elastase/alpha 1-protease inhibitor complexes and as 0.101, 0.119, and 0.143 for lactoferrin. A tendency towards variation of LAC with menstrual cycle in fertile females was noticed. From within-subject variation, between-subject variation and analytical variation, indices of individuality were calculated as 1.1 and 1.8 for elastase/alpha 1-protease inhibitor complexes and lactoferrin, respectively. This means that within-subject variation for lactoferrin is quite small compared to between-subject variation, and the usefulness of reference limits is very limited, when interpreting results from individual patients. For elastase/alpha 1-protease inhibitor complexes, the use of reference limits might be more appropriate, although still not optimal.
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PMID:Within-subject variation of elastase/alpha 1-protease inhibitor complexes and lactoferrin in plasma. 826 8

The inhibitory actions of Ulinastatin, which is a protease inhibitor, on the production of polymorphonuclear leukocyte elastase (PMN-elastase) and interleukin 8 (IL-8) in vascular endothelial cells were evaluated. Our findings suggest that IL-8 plays a role in the production of PMN-elastase. Ulinastatin inhibited the lipopolysaccharide (LPS)-stimulated activity of polymorphonuclear leukocytes (PMN) and the production of IL-8 in vascular endothelial cells. Ulinastatin also inhibited the LPS-stimulated production of PMN-elastase in PMN.
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PMID:The inhibitory actions of protease inhibitors on the production of polymorphonuclear leukocyte elastase and interleukin 8. 827 72

The inhibitory effect of ulinastatin (UST), an intrinsic human trypsin inhibitor was investigated on the activity of polymorphonuclear granulocyte elastase (PMNE) with or without alpha 1-protease inhibitor (alpha 1-PI) using the in vitro models. The results of the dodecyl-sulfate-electrophoresis (SDS-PAGE), indicated that splitting-action of crude granulocyte enzyme solution on the plasma fibronectin was inhibited by concentration-dependent UST of an equivalent value for treatment of stressed state. The PMNE-UST complex was competitively replaced by PMNE-alpha 1-PI complex in vitro models of inflammatory focus and circulation, hence UST was weaker than alpha 1-PI in its binding-affinity for PMNE. The PMNE activity was directly inhibited by UST in the inflammatory focus and circulation with or without alpha 1-PI.
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PMID:[Can ulinastatin be an effective inhibitor of human polymorphonuclear granulocyte elastase under severe stressed state?]. 833 19

To understand the interaction between elastin and elastase, elastin from human aorta was incubated with human leukocyte elastase under conditions favoring proteolysis. Low molecular weight species were separated from the protein fraction by a small centrifuged gel filtration column. The only product of the elastin digest detected on acid polyacrylamide gel electrophoresis was a single band of slower cathodal mobility than human leukocyte elastase alone. This band cross-reacts with antibody to human elastase, indicating that the slow migrating band contains elastase. The putative human leukocyte elastase-elastin-derived peptide complex was treated with hydroxylamine to cleave any possible acyl-enzyme complexes and was then measured for amidolytic activity. Analysis of the amino acid composition of elastin-derived peptide indicates the presence of alanine, glycine, and richness in hydrophobic residues, suggesting that these residues are involved in elastase interaction(s). Incubation of the elastase-elastin-derived peptide with alpha 1-protease inhibitor causes dissociation of the complex and formation of an elastase-alpha 1-protease inhibitor complex. Our results suggest that, locally at the site of proteolysis, elastase activity may be regulated by elastin-derived peptide(s) during elastinolysis.
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PMID:Regulation of neutrophil elastase activity by elastin-derived peptide. 834 32

1. alpha 1-antitrypsin is an antiprotease that inhibits the neutrophil elastase enzyme, and belongs to a family of structurally related serine proteinase inhibitors (serpins). Its methionine358 residue determines the specificity for elastase. 2. The normal M-type alpha 1-antitrypsin is mainly synthesized in the liver parenchymal cells and transported to the plasma. Abnormal Z-mutant alpha 1-antitrypsin is retained in the endoplasmic reticulum, which leads to its intracellular accumulation and to markedly decreased plasma levels. 3. In normal conditions, alpha 1-antitrypsin protects the lungs from destruction by the proteolytic neutrophil elastase. A protease/antiprotease imbalance in the lung is responsible for the development of emphysema in severe alpha 1-antitrypsin deficiency and in cigarette smokers, and accounts for the marked acceleration of the lung disease in smoking alpha 1-antitrypsin deficient patients. Smoking has to be avoided in alpha 1-antitrypsin deficient patients. Replacement therapy with plasma-derived alpha 1-antitrypsin seems indicated in alpha 1-antitrypsin deficient patients with emphysema. 4. Intracellular accumulation of abnormal Z-alpha 1-antitrypsin molecules in liver parenchymal cells may lead to liver disease, ranging from neonatal cholestasis to adulthood cirrhosis and hepatocellular carcinoma. End-stage liver disease can be treated by liver transplantation, which is followed by a phenotypic conversion. 5. Diagnosis of alpha 1-antitrypsin deficiency related disease relies on the presence of a low serum concentration of alpha 1-antitrypsin, and of periodic-acid Schiff positive globules in the liver parenchymal cells. Isoelectric focusing of the serum identifies the protease inhibitor phenotype. The protease inhibitor phenotype is determined by the independent expression of the two parental alpha 1-antitrypsin alleles. It is determinant of the serum level and of the risk for development of lung or liver disease.
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PMID:Alpha 1-antitrypsin deficiency: an overview. 839 99

Cytokine activation of cultured human vascular endothelial cells renders them hyperadhesive for blood leukocytes. Co-incubation of freshly isolated, unstimulated human blood neutrophils with confluent cytokine-activated human endothelial monolayers for 90 minutes results in extensive endothelial detachment and destruction of monolayer integrity. In contrast, unactivated endothelial monolayers remain intact. Using this in vitro model, we have explored the neutrophil-effector mechanisms involved in this injury. Coincubation in the presence of a serine protease inhibitor (phenylmethylsulfonyl fluoride) or specific elastase inhibitors (Ala-Ala-Pro-Val-chloromethyl ketone or alpha-1-protease inhibitor) markedly diminished injury. In contrast, scavengers or inhibitors of oxygen-derived free radicals (superoxide dismutase, catalase, mannitol, or sodium azide) were not protective. Purified human neutrophil elastase mimicked the effect of the neutrophils suggesting a key role for elastase in the neutrophil-mediated injury in this model. Interfering with direct neutrophil-endothelial cell contact by interposing a microporous barrier insert prevented endothelial cell detachment. Furthermore, this neutrophil-mediated detachment could be inhibited with interleukin-8, an action correlated with a decrease in neutrophil adhesion to activated endothelial monolayers. By defining the role of endothelial activation in neutrophil-mediated injury, this in vitro model may provide useful insights into potential therapeutic interventions designed to prevent disruption of the endothelial barrier function.
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PMID:Neutrophil-mediated damage to human vascular endothelium. Role of cytokine activation. 842 50

An ELISA for neutrophil elastase (ELA) in complex with alpha 1-protease inhibitor (PI) (alpha 1-antitrypsin) was developed in microtitre plates and compared to the ELISA kit from MERCK (2-h version). Recovery of ELA-PI was good in both assays. The detection limits were 4.4 micrograms l-1 and 7.7 micrograms l-1 of the in-house and MERCK assay, respectively, while limits of quantitation were estimated to 7.7 micrograms l-1 (5.5-9.9 micrograms l-1) and 28.9 micrograms l-1 (14.6-44.3 micrograms l-1) for the two assays. Furthermore, as dilution curves of normal plasma were parallel with the calibration curve in the in-house assay over a wide range of dilutions, it is feasible to assay plasma in dilutions of only 1:6, resulting in a limit of quantitation of only 1.1 micrograms l-1. The total analytical coefficient of variation for samples measured in double determinations was 10.5%-12.5% in the in-house assay and 13.9%-14.6% in the MERCK assay. One-hundred-and-eight plasma samples covering a wide range of ELA-PI concentrations were analysed in both assays. A proportional difference between the two methods was detected, the mean ratio (in-house/MERCK) with 95% confidence limits was 1.115 (1.070-1.160). The cause of the difference was probably due to difference calibration of the assays. Until this problem is solved, method specific reference intervals are needed. A reference interval for the in-house method based on plasma samples from 123 healthy adults; median age 36 years (range: 19-65 years) was estimated to 16.5-48.5 micrograms l-1.
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PMID:An ELISA for elastase alpha 1-protease inhibitor complexes in human plasma and serum. 846 13

In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.
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PMID:Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. 852 Jul 85

Human monocyte/neutrophil elastase inhibitor (HEI) is a protease inhibitor of the serpin superfamily that rapidly inactivates neutrophil elastase, proteinase-3, and possibly cathepsin-G in vitro and, by regulating these potent proteases, is thought to prevent tissue damage at inflammatory sites. The HEI gene (ELANH2) was characterized by amplifying intron regions using cDNA-specific primers. Intron positions of ELANH2 were found to be homologous to intron positions in the genes for the serpin molecules chicken ovalbumin and human plasminogen activator inhibitor-2 (PLANH2). Because serpin superfamily genes in general have widely different organizational patterns, the shared organization of these genes strengthens the evidence that they form a subgroup or family, the "ovalbumin-related serpin" ("Ov-serpin") family. By amplifying DNA of a somatic cell hybrid panel, ELANH2 was unambiguously localized to chromosome 6. The use of a panel of radiation and somatic cell hybrids specific for chromosome 6 refined the localization of ELANH2 to the short arm telomeric of D6S89, F13A, and D6S202 at 6p24-pter. Another Ov-serpin gene PI6 (placental thrombin inhibitor) was colocalized to the same region, thus defining an Ov-serpin locus on chromosome 6 in addition to the previously defined PLANH2-containing Ov-serpin locus on chromosome 18.
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PMID:Characterization and chromosomal localization of ELANH2, the gene encoding human monocyte/neutrophil elastase inhibitor. 853 31


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