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)

Serum and granulocyte elastase-type protease activities were determined simultaneously with their main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy control and atherosclerotic (ATS) subjects. The age-related associations of these parameters were also investigated. Serum elastase-type protease activity increased, but not statistically significantly, with aging in both control and ATS subjects. The enhancement of elastase-type protease activity in sera of ATS patients was significantly (p less than .02) greater than control subjects only in the case of the elderly. The granulocytes' elastase activity was significantly greater in granulocytes derived from both middle-aged and elderly ATS patients (p less than .03 and p less than .06) compared to age-matched control subjects. Alpha-1-antitrypsin was not significantly lower, whereas alpha-2-macroglobulin was significantly lower in sera of ATS subjects compared to age-matched control subjects (p less than .01). The conclusion is that increased elastase-type activity and decreased antiproteinase activity should be considered as potential factors in atherosclerotic arterial wall damage. The similarity of the results in the elderly and the ATS subjects suggest that atherosclerosis is an early aging process.
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PMID:Sera and leukocyte elastase-type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages. 138 Sep 68

We characterized the elastase and antielastase activity of the alveolar fluid of seven patients with the adult respiratory distress syndrome (ARDS) and thirteen normal volunteers. Alpha-1-antitrypsin (A1AT) concentrations were 60-fold higher in ARDS as compared to normal lavage fluid (2,140 +/- 498 nM; 36.1 +/- 4.2 nM, respectively). ARDS fluid antineutrophil elastase activity was also considerably higher than that of normals (979 +/- 204 nM; 31.3 +/- 2.9 nM, respectively). Despite the antineutrophil elastase excess, 5 of 7 ARDS lavage samples contained elastase activity (mean, 6.1 +/- 2.4 pM) as assayed using low-molecular-mass substrate, while only 1 of 13 normal subjects had detectable elastase activity (0.2 pM) (P less than 0.01, compared with ARDS). That this activity was due to alpha-2-macroglobulin (A2MG)-complexed neutrophil elastase was evidenced by (a) the Sephadex G-75 elution profile; (b) the inactivity against insoluble [3H]elastin; (c) the inhibitory profile with phenylmethylsulfonyl fluoride, methoxy-succinyl-alanyl-alanyl-prolyl-valyl-chloromethylketone, ethylene diamine tetraacetic acid, and A1AT; and (d) the immobilization by A2MG antibody bound to polystyrene plates. Furthermore, in agreement with the predicted affinity of A1AT and A2MG for neutrophil elastase, the ratio of A2MG to A1AT in the fluid (0.57%) coincided with the ratio of the A2MG- to A1AT-complexed elastase (0.36%). These findings suggest that the net lung protease-antiprotease balance in ARDS is shifted largely in favor of the antiproteases (chiefly A1AT), and that the antiproteases, A1AT and A2MG, have similar affinities for neutrophil elastase in vivo.
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PMID:Alveolar fluid neutrophil elastase activity in the adult respiratory distress syndrome is complexed to alpha-2-macroglobulin. 245 60

Instillation of human neutrophil elastase (HNE) into hamster lungs produces milder emphysema but more pulmonary hemorrhage than an equivalent amount of porcine pancreatic elastase (PPE), whether equivalence is determined by elastolytic units or moles. We undertook a study of the mechanisms of these differences. 125I-HNE or 3H-PPE were instilled intratracheally into hamsters. The partitioning of radioactivity between bronchoalveolar lavage fluid (BAL) and lung tissue was similar for HNE and PPE as were the half-lives, 45 and 51 min, respectively, for uncomplexed, enzymatically active HNE and PPE. In BAL there was preferential binding and inactivation of HNE by the hamsters' alpha-1-protease inhibitor (a-1-PI) whereas PPE was preferentially bound by alpha-2-macroglobulin (a-2-M). This was also observed in vitro when HNE and PPE were incubated with plasma from untreated hamsters. Nevertheless, when the sum of the elastase binding capacity of a-1-PI and a-2-M was considered, hamster plasma had similar binding capacities for HNE and PPE. It is known that the enzymatic activity of elastases is inhibited by formation of a stable complex with a-1-PI. On the other hand, elastases bound to a-2-M are protected against a-1-PI inhibition but can free themselves by proteolysis and exhibit elastolytic activity. Preferential inactivation of HNE by a-1-PI may be one mechanism that accounts for the lesser emphysema-inducing potency of HNE than of PPE.
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PMID:Defenses of the hamster lung against human neutrophil and porcine pancreatic elastase. 246 16

Inflammatory diseases may lead to local tissue injury due to an imbalance between leukocyte elastase and protease inhibitors (alpha-1-antitrypsin, alpha-2-macroglobulin). Hence, we determined the plasma level of elastase in patients with chronic tonsillitis using an enzyme-linked immunoassay and compared the results with those obtained from controls. There was a significant elevation of leukocyte elastase in patients with chronic inflammation of the tonsils compared with our controls. The sensitivity and specificity of the elastase assay characterise this method as a reliable one. Hence, the determination of leukocyte elastase in peripheral blood can be useful if the indication for tonsillectomy is in question.
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PMID:[Behavior of leukocyte elastase in chronic inflammatory tonsillar diseases]. 247 3

Triggered human neutrophils were able to maintain released elastase in an active form in the presence of purified alpha-1-proteinase inhibitor (alpha-1-PI), serum or bronchoalveolar lavage fluid (BAL). The accumulation of free elastase activity was associated with a decrease in the ability of the alpha-1-PI to inhibit porcine pancreatic elastase, an increase in proteinase activity associated with alpha-2-macroglobulin, and the oxidation of alpha-1-PI to a molecule containing four methionine sulfoxide residues. Neutrophils used both hypochlorous acid and long-lived N-chloroamines to oxidize the alpha-1-PI, but hypochlorous acid was preferentially used for suppressing the activity of the antiproteinase over short distances whereas the N-chloroamines were effective even when the phagocytes and alpha-1-PI were physically separated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified alpha-1-PI, serum, or BAL that had been incubated with triggered neutrophils revealed that the released neutrophil elastase was not complexed with the antiproteinase and that a portion of the alpha-1-PI had undergone proteolysis. These data suggest that the presence of free neutrophil elastase as well as inactive, oxidized, and proteolyzed alpha-1-PI in fluids recovered from inflammatory sites in vivo could be directly mediated by triggered neutrophils alone.
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PMID:Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions. 351 84

Human lung elastin has been isolated by both a degradative and nondegradative procedure and the products obtained found to have amino acid compositions comparable to published results. These elastin preparations, when utilized as substrates for various mammalian proteinases, were solubilized by porcine elastase at a rate six times faster than human leukocyte elastase. Leukocyte cathepsin G also solubilized lung elastin but only at 12% of the rate of the leukocyte elastase. In all cases the elastin prepared by nondegradative techniques proved to be the best substrate in these studies. The differences in the rate of digestion of elastin of the two elastolytic proteinases was readily attributed to the specificity differences of each enzyme as judged by carboxyterminal analysis of solubilized elastin peptides. The plasma proteinase inhibitors, alpha-1-proteinase inhibitor and alpha-2-macroglobulin abolished the elastolytic activity of both leukocyte enzymes, while alpha-1-antichymotrypsin specifically inactivated cathespsin G. Two synthetic inhibitors, Me-O-Suc-Ala-Ala-Pro-Val-CH2Cl (for elastase and Z-Gly-Leu-Phe-CH2Cl (for cathepsin G) were equally effective in abolishing the elastolytic activity of the two neutrophil enzymes. However, inhibition of leukocyte elastase by alpha-1-proteinase inhibitor was significantly suppressed if the enzyme was preincubated with elastin prior to addition of the inhibitor.
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PMID:The degradation of human lung elastin by neutrophil proteinases. 615 74

The Semi-alkaline proteinase (Seaprose) from Aspergillus melleus has been tested for its ability to either inactivate or form complexes with three human plasma proteinase inhibitors, alpha-2-macroglobulin, alpha-1-antichymotrypsin and alpha-1-proteinase inhibitor. alpha-2-Macroglobulin was found to inhibit Seaprose, with two mol of enzyme being complexed per mol of inhibitor. However, alpha-1-proteinase inhibitor was rapidly inactivated by the fungal enzyme as a result of cleavage of the inhibitor, primarily at the P1-P'1 reactive site. Curiously, alpha-1-antichymotrypsin was found to form complexes with Seaprose and also be inactivated by this inhibitor. Apparently, the enzyme can recognize two sites within the reactive site loop of the inhibitor, one at the P4-P'5 position, resulting in inactivation, and one presumably at the P1-P'1 reactive site which results in complex formation. The fact that Seaprose can so rapidly inactivate alpha-1-proteinase inhibitor, the primary regulator of neutrophil elastase, indicates that Seaprose would be a rather poor choice for therapy in individuals with bronchial mucus hypersecretion.
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PMID:Interactions of alpha-1-antichymotrypsin, alpha-1-proteinase inhibitor, and alpha-2-macroglobulin with the fungal enzyme, seaprose. 752 Nov 71

Biochemically, there is usually much less elastase activity in gingival tissue than in crevicular fluid. The tissue distributions of active and inactive elastase and the endogenous inhibitors alpha-1-proteinase inhibitor (alpha 1PI) and alpha-2-macroglobulin (alpha 2M) were therefore compared. Inflamed tissue was obtained from chronic periodontitis patients, and cryostat sections were incubated with the histochemical elastase substrate MeOSuc-Ala-Ala-Pro-Val-MNA. Adjacent sections were examined immunocytochemically with antibodies to neutrophil elastase, alpha 1PI, alpha 2M, and leukocyte differentiation antigens. Antigenic elastase was widely distributed in CD15-positive granulocytes in both the epithelium and lamina propria as well as in granulomatous tissue from infrabony defects. However, there was very limited histochemical staining of these cells, and biochemical activity against the equivalent substrate MeOSuc-Ala-Ala-Pro-Val-AFC could be extracted only from sections with such staining. The pH optimum and effector response of the activity in the extracts were, nevertheless, consistent with those of leukocyte elastase. The large difference between the total elastase content of the tissue, as determined immunocytochemically, and the limited amount of active enzyme, as demonstrated histochemically, indicated that the majority was in an inactive form. The involvement of tissue inhibitors was suggested by the fact that extracts from sections with no histochemical staining reduced biochemical elastase activity in crevicular fluid. alpha 2M was found in many fibroblasts and also some CD68-positive macrophages, which additionally contained alpha 1PI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Localization of active and inactive elastase, alpha-1-proteinase inhibitor, and alpha-2-macroglobulin in human gingiva. 753 62

The purpose of this study was to assess the recovery of certain proteins from paper strips used for sampling of gingival crevicular fluid (GCF). During a period of 60 min, proteins were eluent in isotonic phosphate-buffered saline, pH 7.4, without detergent. This eluent did not lyse neutrophils applied to the strips, which might otherwise contribute intracellular substances-, e.g., elastase to the GCF samples. The proteins applied (MW 12-725 kD) were satisfactorily recovered (about 90%). However, free neutrophil elastase, unlike elastase complexed with alpha-2-macroglobulin, could not be recovered from the paper strips. Strips made of polyvinylidene difluoride (Durapore) were also tested and 31% of the applied pure elastase was recovered from them. A comparison of measurements made with a Periotron 6000 on Periopaper and Durapore strips, showed that the values obtained with Durapore were too low for accurate measurements of small volumes of fluid. On the whole, when the elution was made in isotonic buffers at neutral pH and without detergents, the recovery of most proteins was satisfactory and reproducible, and independent of MW in the tested range. However, the study also showed poor recovery of uncomplexed elastase.
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PMID:Methodological considerations in GCF sampling with paper strips: poor recovery of uncomplexed elastase. 878 47

Proteases present in oral fluid effectively modulate the structure and function of some salivary proteins and have been implicated in tissue destruction in oral disease. To identify the proteases operating in the oral environment, proteins in pooled whole saliva supernatant were separated by anion-exchange chromatography and individual fractions were analyzed for proteolytic activity by zymography using salivary histatins as the enzyme substrates. Protein bands displaying proteolytic activity were particularly prominent in the 50-75 kDa region. Individual bands were excised, in-gel trypsinized and subjected to LC/ESI-MS/MS. The data obtained were searched against human, oral microbial and protease databases. A total of 13 proteases were identified all of which were of mammalian origin. Proteases detected in multiple fractions with cleavage specificities toward arginine and lysine residues, were lactotransferrin, kallikrein-1, and human airway trypsin-like protease. Unexpectedly, ten protease inhibitors were co-identified suggesting they were associated with the proteases in the same fractions. The inhibitors found most frequently were alpha-2-macroglobulin-like protein 1, alpha-1-antitrypsin, and leukocyte elastase inhibitor. Regulation of oral fluid proteolysis is highly important given that an inbalance in such activities has been correlated to a variety of pathological conditions including oral cancer.
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PMID:Activity-based mass spectrometric characterization of proteases and inhibitors in human saliva. 2001 83


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