Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that two polymorphonuclear neutrophil (PMN)-derived proteinases, namely cathepsin G (Cat. G) and elastase (HLE), acting in synergy activated nearby platelets in vitro. This cellular interaction could result in a pathology such as the adult respiratory distress syndrome (ARDS). Since elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were detected in these patients and therefore could be involved in this disease, we looked for their effects in the PMN-platelet cooperation system. Addition of IL-8 to mixed suspensions of PMN and platelets induced weak but significant platelet aggregations. Upon preincubation with TNF-alpha, aggregations triggered by IL-8 were significantly increased. The targets of these cytokines were not the platelets but the PMNs. This was shown by following beta-glucuronidase release and more interestingly by measuring the enzymatic activities of Cat. G and HLE in the supernatant. Inhibition of the platelet response upon addition of a serine proteinase inhibitor, eglin C, clearly demonstrated the involvement of these two enzymes. Taken together, these results constitute an additional argument for the role of the PMN-platelet interaction in ARDS.
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PMID:Synergism between interleukin-8 and tumor necrosis factor-alpha for neutrophil-mediated platelet activation. 788 Sep 76

Anti-neutrophil cytoplasmic antibodies (ANCA) are antibodies directed against enzymes that are found mainly within the azurophil or primary granules of neutrophils. There are 3 types of ANCA that can be distinguished by the patterns they produce by indirect immunofluorescence when tested on normal ethanol-fixed neutrophils. Diffuse fine granular cytoplasmic fluorescence (cANCA) is typically found in Wegener's granulomatosis, in some cases of microscopic polyarteritis and Churg Strauss syndrome, and in some cases of crescentic and segmental necrotising glomerulonephritis, but it is rare in other conditions. The target antigen is usually proteinase 3. Perinuclear fluorescence (pANCA) is found in many cases of microscopic polyarteritis and in other cases of crescentic and segmental necrotising glomerulonephritis. These antibodies are often directed against myeloperoxidase but other targets include elastase, cathepsin G, lactoferrin, lysozyme and beta-glucuronidase. The third group designated "atypical" ANCA includes neutrophil nuclear fluorescence and some unusual cytoplasmic patterns, and while a few of the target antigens are shared with pANCA, the others have not been identified. Sera that produce a pANCA or atypical ANCA pattern on alcohol-fixed neutrophils result in cytoplasmic fluorescence when formalin acetone fixation is used. pANCA or atypical ANCA occur in about 2/3 of all individuals with ulcerative colitis or primary sclerosing cholangitis, and they are found in a third of patients with Crohn's disease. The reported incidence of ANCA in rheumatoid arthritis and SLE varies considerably but the patterns are predominantly pANCA and atypical ANCA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-neutrophil cytoplasmic antibodies (ANCA): their detection and significance: report from workshops. 809 May 92

The effect of glycosaminoglycans (GAGs) such as sulodexide, low molecular mass dermatan sulfate, heparin and some derivatives with different degrees and types of sulfation was studied on cathepsin G- or thrombin-stimulated platelets and n-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated polymorphonuclear leucocytes (PMNs). All GAGs (0.01-20 micrograms/mL) inhibited both platelet aggregation induced by cathepsin G and its catalytic activity. Thrombin-induced platelet aggregation in contrast was only prevented by heparin, sulodexide and dermatan (2-100 micrograms/mL). All GAGs, except 2-O,N-desulfated heparin, inhibited beta-glucuronidase and lysozyme release, as well as beta-glucuronidase activity and PMN superoxide production by the peptide fMLP. The efficacy of GAGs was clearly dependent on the degree and type of sulfation since dermatan and N-desulfated heparins were comparatively less effective. The observation that heparin and other GAGs inhibit platelet activation induced by the PMN protease cathepsin G may help determine whether mechanisms of action other than anticoagulation are critical in the antithrombotic activity of heparin and related compounds.
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PMID:Effects of glycosaminoglycans on platelet and leucocyte function: role of N-sulfation. 837 48

The in vitro effect of unfractionated heparin and dermatan sulfate, as well as oligo-heparin and oligo-dermatan sulfate, on human PMN function was investigated. Superoxide anion generation in fMLP-stimulated PMN was dose-dependently reduced by heparin and oligo-heparin, while DS and oligo-DS lacked inhibitory activity. FMLP-stimulated PMN adhesion to endothelial cells was reduced to a similar extent by both heparin and oligo-heparin, but not by DS and oligo-DS. On the other hand, none of the compounds affected the adhesion of unstimulated PMN to either IL-1- or PMA-activated endothelial cells. Heparin and oligo-heparin also inhibited the homotypic aggregation of fMLP-stimulated PMN. As reported, coincubation of platelets with fMLP-stimulated PMN resulted in platelet activation, a process mainly mediated by the PMN-derived serine protease cathepsin G. Both heparin and DS, as well as their oligo-derivatives, reduced platelet activation induced by either fMLP-stimulated PMN or purified leukocytic cathepsin G. Finally, besides cathepsin G, also the activity of beta-glucuronidase and lysozyme released by stimulated PMN were reduced by heparin, oligo-heparin and DS. These data support the hypothesis that heparin and other GAGs may exert an antiinflammatory role.
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PMID:Effect of heparin, dermatan sulfate, and related oligo-derivatives on human polymorphonuclear leukocyte functions. 843 35

Recombinant adenoviruses expressing human beta-glucuronidase (AxCAhGUS) and CTLA-4Ig (AxCACTLA-4Ig) were generated and therapeutic efficacy was investigated using a murine model of mucopolysaccharidosis type VII (MPSVII). Seven days after the intravenous administration of AxCAhGUS, high levels of beta-glucuronidase (GUSB) activity were observed in the liver, spleen, heart, lung, kidney, and serum, while viral DNA was predominantly detected in the liver. To investigate the contribution of in vivo cross-correction of GUSB between the liver and other organs, we injected the serum obtained from the transduced mice into untreated MPSVII mice. Similar distributions of GUSB activity were observed in the serum-injected mice, suggesting that GUSB activities detected in the extrahepatic organs were due to the cross-correction rather than the direct gene transduction. This result also suggested that maintaining high levels of GUSB in the systemic circulation was essential for the effective treatment of MPSVII. To achieve this, we injected AxCAhGUS and AxCACTLA-4Ig into MPSVII mice. Serum GUSB activity was sustained at high levels for more than 200 days and morphological normalization of the liver and spleen was observed for a year. This suggests that long-term therapeutic efficacy in visceral organs of MPSVII is achievable by coexpression of CTLA-4Ig through an in vivo cross-correction pathway.
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PMID:Adenovirus-mediated gene therapy for mucopolysaccharidosis VII: involvement of cross-correction in wide-spread distribution of the gene products and long-term effects of CTLA-4Ig coexpression. 1093 61

Circulating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulation with other stimuli like N-formyl-methionyl-leucyl-phenylalanine (FMLP), interleukin-8 (IL-8), leukotriene B4 (LTB4), or platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). In this study, we raised the question whether factors released from polymorphonuclear leukocytes (PMNs) can specifically down-regulate C5a-dependent neutrophil functions. When neutrophils were preincubated with either neutrophil lysates or neutrophil degranulation supernatants, a complete inhibition of C5a-stimulated beta-glucuronidase release and chemotaxis could be observed, whereas FMLP-, IL-8-, LTB4- or PAF-dependent functions were not affected. Serine protease inhibitors like phenylmethylsulfonyl fluoride, antileukoprotease, or elafin abolished this effect. High-performance liquid chromatography of neutrophil degranulation supernatants revealed pronounced inhibition of C5a-dependent neutrophil functions in fractions exerting elastase or cathepsin G activity, but not in fractions exerting proteinase 3 activity. Using purified human leukocyte elastase (HLE), C5a responses like intracellular calcium influx, beta-glucuronidase release, and chemotaxis were also specifically inhibited. Our experiments show that the release of HLE or cathepsin G from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin G may therefore play an important role in the down-regulation of acute inflammation.
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PMID:Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis. 1514 22

Treatment of nonmalignant childhood disorders by bone marrow transplantation (BMT) is limited by toxicity from preparatory regimens and immune consequences associated with engraftment of allogeneic donor cells. Using costimulatory blockade (anti-CD40L mAb and CTLA-4Ig) combined with high-dose BMT in nonablated neonates, we obtained engraftment and established tolerance using both partially MHC mismatched (H2g7 into H2b) and fully mismatched BM (H2s into H2b). Recipients were mucopolysaccharidosis type VII (MPS VII) mice with lysosomal storage disease in order to assess therapeutic outcome. Recipients treated with donor lymphocyte infusion (DLI) amplified microchimerism to full donor. Recipients without DLI maintained long-term engraftment, tolerance, and had extended life spans. DLI increased donor cell mediated replacement of beta-glucuronidase (GUSB) activity in all tissues and maintained clearance of lysosomes better than in non-DLI-treated mice. DLI amplification of partially mismatched BM and fully mismatched BM caused late onset chronic GvHD in 56% and 100% of recipients, respectively.
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PMID:Attenuation of murine lysosomal storage disease by allogeneic neonatal bone marrow transplantation using costimulatory blockade and donor lymphocyte infusion without myeloablation. 1648 52


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