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

Cervical maturation, dilatation and uterine contraction in imminent premature delivery are closely related to chemical mediators from activated granulocytes which infiltrate into the cervix. It is known that urinastatin (urinary trypsin inhibitor, UTI) inhibits many kinds of chemical mediators from granulocytes and macrophages such as granulocyte elastase (elastase) and interleukin 1. We examined the effect of a UTI suppository on uterine contraction and the elastase level in cervical mucus in cases of imminent premature delivery. We treated 43 cases of imminent premature delivery with tocolysis index 3 or 4 with 4 kinds of therapy: Group A (N = 12): ritodorine drop infusion therapy; Group B (N = 9): daily UTI suppository (1,000U) therapy; Group C (N = 14): daily UTI suppository + ritodorine drop infusion therapy; Group D: daily UTI suppository + ritodorine drop infusion + antibiotics (oral cepharosporine) therapy. The elastase level of cervical mucus before treatment was 0.76 +/- 0.40 micrograms/ml in group A, 0.93 +/- 0.43 micrograms/ml in group B, 0.85 +/- 0.40 micrograms/ml in group C and 0.90 +/- 0.41 micrograms/ml in group D. There was no significant difference between these groups. The elastase level in cervical mucus was 0.75 +/- 0.47 micrograms/ml in group A, 0.27 +/- 0.35 micrograms/ml in group B, 0.27 +/- 0.33 micrograms/ml in group C and 0.30 +/- 0.19 micrograms/ml in group D, respectively. The elastase level was decreased significantly in groups B, C and D. The time taken to depress uterine contraction was 65 +/- 66 min in group A, 375 +/- 336 min in group B, 70 +/- 64 min in group C and 58 +/- 53 min in group D, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of granulocyte elastase inhibitor (urinastatin) vaginal suppository on patients with imminent premature delivery]. 134 16

Strong activity of acid-stable trypsin inhibitor (ASTI) was confirmed in some clinical thrombin preparations. Thrombin preparations of human plasma origin had no detectable ASTI activity, whereas some preparations of bovine plasma origin revealed more than 5,000 U/vial (5,000 thrombin units), indicating a higher content of ASTI than of thrombin in terms of protein concentration. Contamination by other biologically active substances was also suggested by variations in amidolytic activity with several synthetic substrates (S-2238, S-2251, S-2444, S-2266 and Bz-L-Arg-pNA). On isoelectric focussing, the ASTI activities migrated in acidic positions with pI values of 3.9, 4.5, 5.0, 5.9 and 6.5, respectively. They were almost parallel to the thrombin Bz-L-Arg-pNA hydrolytic activity, and differed from that of the purified thrombin preparation (pI = 7.0). By gel filtration on Sephadex G-100, the molecular weights of the inhibitors as calculated using standard proteins were 140,000 (main), 70,000 and less than 10,000 (minor), respectively. An immunological difference between the main inhibitor (pI = 3.9, mol wt 140,000) and previously reported plasma ASTI was also confirmed with goat anti-UTI serum by the double immunodiffusion and ELISA methods. The inhibitor exerted a strong inhibitory effect not only on trypsin and chymotrypsin, but also on non-plasmic fibrinolysis with human leukocyte elastase, and to a lesser extent on the blood coagulation system (lengthening of APTT and PT). Clearly, when using thrombin preparations and analyzing the data obtained after their administration, the effects of this and other contaminant biologically active substances must be taken into account.
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PMID:Strong activity of acid-stable trypsin inhibitor in bovine thrombin for clinical use. 314 Oct 90

To investigate the inhibitory effect of serine protease inhibitors (SPI) on neutrophil-mediated endothelial cell (EC) injury, we analyzed the in vitro cytotoxicity of radiolabeled human umbilical vein EC (HUVEC) mediated by neutrophils in the presence of SPI. The EC injury was inhibited dose-dependently by urinary trypsin inhibitor (ulinastatin, UTI) and ONO-5046, which have the ability to inactivate neutrophil elastase, but not by gabexate mesilate, nafamostat mesilate, aprotinin, and argatroban, which have no ability to inactivate neutrophil elastase. In addition, when UTI and ONO-5046 were added to the tumor necrosis factor alpha-primed neutrophils alone, they showed a dose-dependent inhibition of the intracellular elastase activity, but the other SPI did not, for either flow cytometry or confocal microscopy. Therefore, UTI and ONO-5046 may protect EC against the neutrophil-mediated injury not only by inactivating the extracellular elastase secreted by neutrophils, but also by acting directly on neutrophils and suppressing the production and secretion of activated elastase from them.
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PMID:Inhibitory effect of serine protease inhibitors on neutrophil-mediated endothelial cell injury. 1127 74

The aim of this study was to assess the contribution of physiological protease inhibitors (urinary trypsin inhibitor [UTI] and alpha 1-antitrypsin [alpha 1AT]) to the inhibition of trypsin and human leukocyte elastase (HLE) activities, to examine whether UTI and UTI-trypsin complexes compete for binding of alpha 1AT-HLE complexes to human neutrophils and promyeloid leukemia U937 cells, and to determine whether the modified ligands for the serpin-enzyme complex (SEC) receptor have neutrophil chemotactic activity. UTI is a strong inhibitor for trypsin and HLE and is relatively resistant to inactivation by trypsin,while the decline in inhibitor activity of alpha 1AT proceeds faster by trypsin. UTI protects the inactivation of alpha 1AT by trypsin. The SEC receptor mediates neutrophil chemotactic activity of alpha 1AT-HLE complexes. UTI and UTI-trypsin complexes failed to bind to the SEC receptor on neutrophils, and they did not inhibit alpha 1AT-HLE complexes-mediated neutrophil chemotactic activity. When alpha 1AT treated with trypsin was incubated with HLE, neutrophil chemotactic activity was inhibited. In the presence of UTI, however, UTI protected neutrophil chemotaxis mediated through SEC receptor. The present study suggests another working hypothesis that, besides the effects on anti-protease activity, UTI plays an important role in inhibition of inactivation/degradation of alpha 1AT by trypsin and in protection of neutrophil chemotaxis.
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PMID:Urinary trypsin-inhibitor protects neutrophil chemotaxis in the inflammatory response. 2155 9