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)

Human neutrophil elastase degraded tropoelastin approximately 9 times faster than it did solubilized elastin and approximately 19 times faster than it did lung elastin. When bound to alpha2-M, the enzyme retained approximately 6 per cent of its activity toward tropoelastin and solubilized latter observations suggest that alpha2-M--bound elastase, cleared slowly from lung extracellular tissue space, may participate normally in the turnover of soluble precursor (s) of elastin and may contribute to the development of emphysema in alpha1-antitrypsin deficiency.
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PMID:Degradation of tropoelastin and elastin substrates by human neutrophil elastase, free and bound to alpha2-macroglobulin in serum of the M and Z (Pi) phenotypes for alpha1-antitrypsin. 8 40

We assayed protease and elastase activity of lysosomal granules of purified neutrophil suspensions in 58 patients with chronic irreversible airflow obstruction and compared them to 26 healthy control subjects. Denatured hemoglobin and tritiated elastin were used as substrates for protease and elastase assays. Forty-two patients had M antitrypsin phemotype, five had MS, and 11 had Z variant (five were homozygotes and six were heterozygotes). We did not find significant differences in mean lysosomal elastase or protease activity between patients with normal antitrypsin and control subjects; however, a few patients had concentrations of neutrophil elastase that exceeded the range among control subjects. There was no significant correlation between neutrophil protease or elastase activity and age, smoking, degree of airway obstruction, diffusing capacity, lung elastic recoil, or radiologic presence of emphysema in patients with M and MS antitrypsin. In patients with Z variant antitrypsin, protease and elastase concentrations per unit of lysosomal protein were not significantly different from those in control subjects or M patients; however, both elastase and protease content per 108 neurtophils was significantly higher in homozygous and heterozygous Z patients as compared to normalsubjects and M patients, which suggest an increase in the neutrophil content of protease and elastase in patients with Z antitrypsin deficiency. These results suggest that hte concentrations of protease and elastase in neutrophils do not appear to interact as additive risk factors in the pulmonary impairment of most patients with chronic airflow obstruction, but may be of importance as risk factors in patients with Z or MZ phenotype and in a few patients with M phenotype.
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PMID:Interrelationships between neutrophil elastase, serum alpha, -antitrypsin, lung function and chest radiography in patients with chronic airflow obstruction. 31 28

To investigate the role of neutrophil proteases in the pathogenesis of mucus hypersecretion in bronchiectasis, we collected sputum samples from seven patients with bronchiectasis and measured their secretagogue activity by examining secretion of radiolabeled macromolecules by bovine airway submucosal gland cells incubated with sputum supernatants. There was marked secretagogue activity in bronchiectasis sputum, reaching a maximum of 1,963 +/- 292% (mean +/- SEM) above baseline at 1:15 dilution. Addition of ICI 200,355 (10(-5) M), a selective human neutrophil elastase inhibitor, decreased the secretory response markedly (72.53 +/- 5.89% reduction). The combination of aprotinin, an inhibitor of cathepsin G, and ICI 200,355 caused significantly more reduction in the secretory response than ICI 200,355 alone (89.12 +/- 3.8 versus 72.53 +/- 5.89% reduction, p < 0.05). We conclude that bronchiectasis sputum causes a large secretory response from tracheal submucosal glands due mostly to neutrophil proteases.
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PMID:Mucus hypersecretion in bronchiectasis. The role of neutrophil proteases. 128 Sep 28

The purpose of this study was to purify and identify the proteinase-like substance previously recognized as responsible for the Na+/K(+)-ATPase stimulating property of plasma from insulin-dependent diabetic subjects. Anion-exchange chromatography followed by two-step heparin affinity chromatography resulted in a fraction highly enriched in both potent Na+/K(+)-ATPase stimulating activity and potent proteolytic activity. Approx. 400 micrograms of purified protein was isolated from 62 mg of starting plasma proteins. When analyzed on sodium dodecyl sulfate gels the active fraction consisted mainly of one polypeptide band with an apparent molecular mass of 66 kDa under either reducing or nonreducing conditions. The proteinase-like properties of the purified fraction were further revealed by its ability to clot plasma, split fibrinogen with production of fibrinopeptide A and induce shape change in human platelets and irreversible platelet aggregation in the presence of the stable analogue of endoperoxides U46619. Its additional capacity to affect platelet phosphoinositol metabolism was shown by the stimulation of protein kinase C-dependent phosphorylation of 47 kDa platelet membrane protein. In designing an identification protocol for the purified fraction, it was postulated that plasma proteinases are probably bound to their inhibitors, to form a stable covalently linked complex. The possibility that a proteinase-proteinase inhibitor complex was purified instead of single proteinase(s) was investigated. Neither trypsin nor neutrophil elastase were present in the active fraction whereas, among the possible plasma proteinase inhibitors tested, immunoreactivity was observed only in the presence of alpha 1-antitrypsin (alpha 1 AT) antiserum. Double immunodiffusion showed that control human alpha 1 AT and the plasma-purified fraction shared common antigens. Furthermore, both isoelectric focusing and amino acid composition analysis showed that the two substances were similar. The results obtained indicate that alpha 1 AT is apparently the only active component of the purified fraction from the plasma of insulin-dependent diabetics, thus suggesting that an altered form of the inhibitor is responsible for the broad range of proteinase-like effects elicited by the plasma-purified fraction.
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PMID:Purification of proteinase-like and Na+/K(+)-ATPase stimulating substance from plasma of insulin-dependent diabetics and its identification as alpha 1-antitrypsin. 131 11

Studies of both emphysema and adult respiratory distress syndrome (ARDS) support the premise that lung injury is due to unregulated host defense mechanisms. A major mediator of host defense and injury is the neutrophil, which is relatively incapable of regulating its own function. Accordingly, defects in regulatory mechanisms allow neutrophils to damage the lungs. Emphysema serves as a prime example of this link between host defense and injury. Hereditary emphysema is caused by a deficiency in alpha 1-antitrypsin (alpha 1-AT), a protease inhibitor. The decreased levels of this enzyme in affected individuals result in inadequate protection against neutrophil elastase and other proteolytic enzymes, leading to lung damage. Patients with acquired emphysema, associated with cigarette smoking, have normal levels of alpha 1-AT in their lungs. However, the alpha 1-AT in these patients has a reduced ability to associate with and inhibit the action of neutrophil elastase. Thus, both types of emphysema involve an alteration in the balance between proteases and antiproteases. The lung damage observed in patients with ARDS also appears to involve neutrophils, but in this case elastase may not be the culprit. In these patients, neutrophil elastase appears to be inactivated by high levels of alpha 1-AT, thus preventing excess protease action. It is hoped that a more complete understanding of the mechanisms involved in host defense and injury will enable the development of specific therapeutic interventions, such as the alpha 1-AT replacement therapy that is being used to treat patients with hereditary emphysema.
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PMID:Adverse effects of neutrophils on the lung. 132 Mar 28

The in vitro effects of the Pseudomonas aeruginosa-derived phenazine pigments pyocyanin and 1-hydroxyphenazine (1-hp) on neutrophil elastase release and myeloperoxidase-induced inactivation of alpha-1-protease inhibitor (alpha 1-PI) were investigated. 1-hp (6-25 microM), but not pyocyanin, caused a dose-dependent enhancement of elastase release by FMLP:cytochalasin B (CB)-activated human neutrophils. 1-hp (0.78-6.25 microM) also increased the oxidative inactivation of the elastase inhibitory capacity of alpha 1-PI exposed to FMLP:CB-activated neutrophils. Methionine, a scavenger of hypochlorous acid, completely protected alpha 1-PI from inactivation by stimulated neutrophils in the presence or absence of 1-hp. Similar protective effects were observed with sodium azide, an inhibitor of myeloperoxidase. P. aeruginosa-derived 1-hp may promote an elastase-antielastase imbalance in vivo by increasing the release of neutrophil elastase and by enhancing the oxidative inactivation of alpha 1-PI, thereby contributing to the development of tissue destruction in P. aeruginosa-infected patients.
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PMID:Enhanced release of elastase and oxidative inactivation of alpha-1-protease inhibitor by stimulated human neutrophils exposed to Pseudomonas aeruginosa pigment 1-hydroxyphenazine. 132 22

This study was designed to demonstrate the effect of prostaglandin E1 (PGE1) on neutrophil activation in open heart surgery. Twenty adult patients undergoing cardiopulmonary bypass (CPB) for various cardiac operations were divided into 2 groups. PGE1 group consisted of 10 patients (7 males and 3 females) and the control group consisted of 10 patients (6 males and 4 females). In PGE1 group patients, 20-50 ng/kg/min of PGE1 was administered intravenously from the induction of anesthesia to the completion of CPB. Blood samples were taken before, during, after CPB, and in the morning of the first postoperative day. Differential counts of white blood cells, plasma neutrophil elastase (PNEL) activity, serum complements activity (C3a, CH50) and superoxide production of neutrophils were measured. Superoxide production by isolated neutrophils was evaluated utilizing luminol dependent chemiluminescence. After the initiation of CPB complements were activated markedly, and PNEL activity increased significantly in both groups. Although after CPB PNEL activity turned to decrease, it was still significantly higher on the first postoperative day than the preoperative value. There were no significant differences between two groups as for complements activation and PNEL activity. The total number of white blood cells unchanged during CPB and neutrophilia appeared after CPB, but no significant difference between two groups. Superoxide production of neutrophils relatively decreased during CPB and significantly increased after CPB in the control group. However, in PGE1 group superoxide production was reduced after CPB, especially on the first postoperative day. These results showed that PGE1 reduced neutrophil-mediated superoxide production in open heart surgery. In conclusions, PGE1 is useful agent to reduce the hazardous effects of neutrophils after CPB.
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PMID:[Reduction of neutrophil activation by prostaglandin E1 in open heart surgery]. 132 81

Extracellular proteolysis is hypothesized to be the major cause of pulmonary emphysema and oxygen-derived free radicals and neutrophil elastase are thought to play an important role in its pathogenesis. In this study, peripheral polymorphonuclear leukocytes (PMNs) obtained from 16 patients with emphysema generated a significantly larger amount of superoxide and elastase activity than those obtained from normal controls. A significant correlation was observed between elastase activity and superoxide release. In addition, the superoxide release showed a negative correlation with the disease duration. The superoxide release appeared to correlated with a decline of FEV1.0 over the course of several years in 8 patients. It seems likely that activated PMNs play an important role in the development of pulmonary emphysema.
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PMID:The role of free radicals and neutrophil elastase in development of pulmonary emphysema. 133 6

We have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10-60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutrophil elastase potentiates cathepsin G-induced platelet activation. 133 49

IgG is split by neutrophil elastase into Fc and Fab fragments. These IgG fragments influence the functions of stimulated neutrophils such as chemotaxis, oxidative burst, and enzyme release. FMLP stimulated leukocyte chemotaxis is specifically inhibited by the elastase generated Fc fragments. Seven nmol Fc/10(6) PMN totally inhibit the chemotaxis stimulated by 16 to 125 nM FMLP. Native IgG and Fab fragments show no effect. FMLP-stimulated superoxide anion generation is specifically inhibited by Fc fragments with half maximal inhibition by 1.2 nmol/10(6) PMN. The generation of hydrogen peroxide is concomitantly stimulated, resulting in a superoxide dismutase-like effect. FMLP-stimulated elastase and myeloperoxidase release are enhanced by Fab fragments (10 nmol/10(6) PMN) to 206 and 155%, respectively, of reference values by 25 nM FMLP, while Fc and native IgG stimulate to a less extent. Consequently, elastase-generated Fc fragments have an inhibitory effect on inflammation by reducing chemotaxis and oxidative burst of stimulated neutrophils. The release stimulating activity of Fab fragments results in an up-regulation of elastase induced IgG degradation.
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PMID:Regulation of neutrophil functions by elastase-generated IgG fragments. 133 54


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