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)

NO-donor SIN-1 (0.01-1.0 mM) dose-dependently inhibited the basal and FMLP (30.0 mM)-stimulated release of beta-glucuronidase from rat peritoneal leukocytes and antigen-specific stimulation of Interleukin-2 production by T-hybridomas. I-123 LDL binding to human lymphocytes was inhibited by Iloprost (1 mM) but activated by SIN-1 (0.3 mM). We conclude that beside the smooth muscle cells and platelets the blood inflammatory/immune cells are under the PGI2/NO control, however, the precise regulation as well as physiological importance need further investigation.
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PMID:Influence of no-donor (SIN-1) on functions of inflammatory cells. 205 67

Neutrophils (PMNs) may be exposed to high concentrations of biliary products during cholestasis and other hepatic disorders. We have previously reported that bile and certain bile salts enhance superoxide (O2-) release from neutrophils activated with phorbol myristate acetate (PMA) (Dahm et al.: Toxicol. Appl. Pharmacol. 95, 82, 1988), suggesting that PMN oxidative metabolism might be altered in toxicoses or disease states characterized by elevations in serum bile salts and other biliary products. In the present study, we characterized the priming effect of lithocholate for O2- release and also examined the effects of lithocholate on enzyme release from PMNs. PMNs preincubated with lithocholate at concentrations which did not directly stimulate O2- release (3-100 microM) and activated with PMA released greater amounts of O2- than controls exposed to PMA alone, illustrating a priming effect. O2- release from lithocholate-primed PMNs rose sharply between 5 and 10 min after PMA addition and then ceased between 10 and 30 min. The priming effect of lithocholate toward PMA-activated PMNs was reduced approximately 50% by washing PMNs after lithocholate addition and was not dependent on extracellular Ca2+, although removal of Ca2+ from the incubation buffer enhanced the cytotoxicity of lithocholate toward PMNs. In Ca2(+)-supplemented medium, lithocholate primed PMNs for O2- release when formyl-methionyl-leucyl-phenylalanine (FMLP, 10(-8)-10(-6) M) or calcium ionophore, A23187 (10(-7) or 10(-6)M), was used to activate PMNs. Lithocholate (100 microM) by itself had only marginal effects on release of lysozyme or beta-glucuronidase from PMNs. However, lithocholate (100 microM) inhibited beta-glucuronidase release from FMLP-stimulated PMNs to near-baseline levels. When FMLP was added to PMNs prior to lithocholate, beta-glucuronidase release was not reduced as it was when the order of addition was the reverse. Lithocholate had no effect on PMA-stimulated lysozyme release. These results indicate that lithocholate has different actions on PMN O2- release and enzyme release and suggest that lithocholate might exert its action on the PMN plasma membrane.
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PMID:Differential effects of lithocholate on rat neutrophil activation. 211 79

The action of PGE1, PGE2, PGI2 and iloprost on superoxide anion generation, lysosomal enzyme release, and changes of Ca2+ fluxes in human polymorphonuclear leukocytes (PMN) was studied in vitro. Both PGE-type compounds were equipotent inhibitors of FMLP-and PAF-stimulated superoxide anion generation, beta-glucuronidase release (IC50 3-5 mumol/l) and Ca2+ influx while PGI2 and iloprost were ineffective at concentrations up to 10 mumol/l. These inhibitory actions of PGE1 and PGE2 were paralleled by an increase in cAMP level of the PMN while no change occurred with PGI2 and iloprost. None of the prostaglandins affected the initial intracellular Ca2+ liberation after challenge with FMLP or PAF. Preincubation of PMN with PGE1 and PGE2 but not with iloprost resulted in subsequent desensitization against a second administration of these compounds. None of the compounds affected PMN activation produced by arachidonic acid or calcimycin (A 23187). These data demonstrate that PGE-type compounds are effective inhibitors of receptor-mediated (PAF, FMLP) activation of human PMN while prostacyclins are considerably less potent. This suggests that the inhibitory prostaglandin receptor on human PMN belongs to the E-type being functionally different from the inhibitory prostaglandin receptor on human platelets. These results suggest that compounds, such as PGE1 and PGE2 might be superior to prostacyclins to prevent PMN-associated generation of reactive oxygen species and lysosomal enzyme release in situations with endogenous PMN activation, i.e. inflammatory reactions.
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PMID:Cytotoxic enzyme release and oxygen centered radical formation in human neutrophils are selectively inhibited by E-type prostaglandins but not by PGI2. 215 12

Cocaine and its derivatives blunted responses of neutrophils (cell/cell aggregation, up-regulation of the receptor for C3bi (CR3, CD11b/CD18), generation of superoxide anion (O2-) and degranulation to various stimuli. The order of potency of these agents was the same as that for local anesthesia: tetracaine greater than bupivacaine greater than cocaine greater than lidocaine. Neutrophil aggregation elicited by the chemoattractant FMLP (10(-7) M) was inhibited by cocaine (10 mM) to 13.6 +/- 6% of control (p less than 0.002); the IC50 was approximately 4 mM. Cocaine and the other local anesthetics not only inhibited the upregulation of CR3 and O2- generation, but also blocked degranulation of cytochalasin B-treated cells. Cocaine (10 mM) reduced beta-glucuronidase and lysozyme secretion to 4.3 +/- 0.7 and 13 +/- 2.2% controls, respectively; its IC50 was 4 mM. Local anesthetics added after ligand/receptor engagement (FMLP) interrupted aggregation and halted generation of O2-. Moreover, local anesthetics rapidly inhibited aggregation, O2- generation, and degranulation elicited by PMA (1 microgram/ml) or the Ca ionophore A23187 (10 microM): the effects of cocaine could therefore not be attributed to unique actions at the FMLP receptor. Peak levels of intracellular Ca2+ ([Ca]i) at 5 to 10 s, and levels of [Ca]i 120 s after FMLP in Fura 2-loaded cells were significantly lower in cells treated with lidocaine, findings that could be explained by enhanced 45Ca2+ efflux from neutrophils. In cells loaded with bis(carboxyethyl)carboxyfluorescine (pH indicator) local anesthetics failed to affect the initial FMLP-induced (0 to 15 s) drop of pHi but inhibited the later (120 s) realkalinization of the cytosol (lidocaine, bupivacaine). Most remarkably, autoradiographs of SDS gels prepared from stimulated, 32P-labeled neutrophils treated with local anesthetics showed no difference from resting cells, either with respect to patterns of phosphorylation and dephosphorylation or their kinetics. Labeling of a 47-kDa protein, a component of the reduced nicotinamide-adenine dinucleotide phosphate-oxidase system, was unchanged. The effects of local anesthetics, which blunt neutrophil responses without affecting protein phosphorylation, suggest that protein phosphorylation is an insufficient signal for neutrophil activation. Inasmuch as cocaine and its derivatives affect cell functions at sites distal to activation of protein kinase C, these agents should prove useful in uncoupling protein phosphorylation from functional responses.
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PMID:Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase. 216 79

Eosinophil granule major basic protein (MBP) and neutrophils have each been implicated in the inflammatory late phase events of allergic disease. Based on this association and flow cytometric evidence presented in this report for MBP binding to neutrophils, we examined the ability of MBP to activate human neutrophils. Incubation of neutrophils with 0.5 to 3.0 microM MBP at room temperature produced a concentration-dependent chemiluminescence (CL) response that peaked after 50 to 70 min. Reduced-and-alkylated MBP, eosinophil cationic protein, and eosinophil-derived neurotoxin did not induce CL. MBP-induced CL was abrogated in the absence of Ca2+ and was absent in neutrophils isolated from two individuals with chronic granulomatous disease. MBP also stimulated release of superoxide anion (O2-) and lysozyme but not beta-glucuronidase or lactate dehydrogenase. Additionally, 1.5 microM MBP in combination with FMLP or platelet-activating factor stimulated a synergistic increase in O2- release from cytochalasin B-treated neutrophils. The degree of synergism with FMLP or platelet-activating factor was inversely related (p less than 0.005) to the level of MBP-induced O2- release. These results indicate that MBP activates neutrophils in a noncytolytic fashion and provide evidence that eosinophil-neutrophil collaboration may contribute to the pathogenesis observed in allergic late phase reactions.
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PMID:Noncytotoxic activation of neutrophils by eosinophil granule major basic protein. Effect on superoxide anion generation and lysosomal enzyme release. 217 May 21

The tissue destruction resulting from release of lysosomal enzymes by exocytosis and degranulation of polymorphonuclear leucocytes in host gingiva may contribute significantly to periodontal diseases. In this investigation peripheral blood was obtained from healthy controls and otherwise healthy individuals with rapidly progressive periodontitis. Polymorphonuclear leucocytes were isolated and suspended in HBSS for subsequent in vitro FMLP challenge to induce degranulation. The supernatant was tested for beta-glucuronidase. Polymorphonuclear leucocytes from patients with rapidly progressive periodontitis contained significantly higher absolute amounts of beta-glucuronidase (p less than 0.001) and released greater amounts at various molarities of FMLP antigenic challenge (p less than 0.01). Such an increase in lysosomal enzyme activity may provide an enhanced potential for tissue destruction in this periodontal disease.
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PMID:Increased intracellular levels of beta-glucuronidase in polymorphonuclear leucocytes from humans with rapidly progressive periodontitis. 237 86

A synthetic peptide, AVLPRSAKEL (LU10), the N-terminal amino acid sequence of chemotactic protein (LUCT/IL-8), showed chemotactic activity to polymorphonuclear leukocytes (PMN) with an ED50 of 5 nM for comparable to that of LUCT. Native LUCT and LU10 specifically induced the phosphorylation of 64 kD protein of PMN, and serine residue in the 64 kD protein was major phosphorylated amino acid. Furthermore, native LUCT enhanced the release of myeloperoxidase and beta-glucuronidase from PMN in the presence of cytochalasin B and FMLP, but LU10 did not. These results strongly suggest that the active site for both chemotactic stimulation and 64 kD protein phosphorylation is localized on the sequence of N-terminal 10 amino acids of LUCT.
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PMID:Localization of chemotactic activity and 64 kD protein phosphorylation for human polymorphonuclear leukocytes in N-terminus of the chemotactic protein LUCT/IL-8. 267 39

The effects of pertussis toxin (PT) on human neutrophil responses mediated by the 42-kDa IgG Fc R (Fc gamma R42) were compared with its effects on responses mediated by the FMLP receptor. Pre-treatment of neutrophils with PT completely inhibited FMLP stimulation of superoxide production and blocked over 95% of FMLP-stimulated degranulation. PT inhibited superoxide production stimulated by Fc gamma R42 cross-linking by 92%. In contrast, degranulation stimulated by Fc gamma R42 was only partially inhibited, with beta-glucuronidase release inhibited by 54%, lysozyme by 33%, and lactoferrin by 78%. With either stimulus, PT inhibition was maximal in the range from 1.8 to 2 micrograms/ml. Responses to both stimuli declined in a parallel fashion with increasing time of exposure to PT with maximal inhibition occurring after 2 h of exposure. Inhibition of FMLP responses and Fc gamma R42-mediated superoxide production, but not degranulation, correlated with ADP-ribosylation of a 45-kDa membrane protein. Inhibition by PT of Fc gamma R42-mediated responses was not due to a change in receptor number. These data suggest that activation of polymorphonuclear neutrophils via Fc gamma R42 proceeds through two pathways, only one of which is regulated by a PT-sensitive G protein.
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PMID:Pertussis toxin inhibits human neutrophil responses mediated by the 42-kilodalton IgG Fc receptor. 296 66

Polymorphonuclear leukocytes isolated from endotoxin pretreated (0.1 mg/kg 24 hours before) guinea pigs are shown to be hypersensitive and hyperresponsive to the formylated bacterial chemoattractant FMLP in vitro. Dose-response curves for chemiluminescence and beta-glucuronidase release are shifted to the left and maxima are increased. In receptor binding studies the FMLP binding capacity is shown to be enhanced in cells from endotoxin pretreated animals. FMLP (0.3 mg/kg) administered intravenously into anaesthetized and artificially ventilated guinea pigs is shown to induce neutropenia and a biphasic rise of the insufflation pressure. This response is exaggerated in endotoxin pretreated animals. The initial elevation of the airway resistance is cyclooxygenase dependent, whereas the following rise is cyclooxygenase independent and parallels the neutropenia. Histologically PMN's are shown to be trapped in the pulmonary capillaries. This is associated with an intraseptal/interstitial edema. The results illustrate a functional synergism between two important bacterial products, endotoxin and FMLP.
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PMID:Endotoxin pretreatment enhances neutrophil FMLP-receptor binding and activity in guinea pigs. 311 69

Chemotactic migration, production of superoxide anion (O2-), and the release of beta-glucuronidase from azurophilic granules were determined in polymorphonuclear leukocytes (PMN) from 135 patients with infectious (e.g., pyoderma, acne conglobata, erysipelas) as well as noninfectious (psoriasis) skin diseases. Purified C5a and the formylated tripeptide FMLP were used as stimuli. In addition, longitudinal profiles of PMN activities were performed at daily intervals in several patients. There was a complete absence of PMN responses (chemotaxis, O2--production, and enzyme release) specifically induced by C5a in 25 patients suffering from various inflammatory diseases of the skin. In these patients PMN responsiveness for the tripeptide FMLP was either normal or increased. The C5a-dependent defect of PMN was transient and correlated with disease activity. When normal PMN were incubated with sera from C5a-defective patients, no inherent stimulatory or inhibitory activities compared to control sera were seen. Pretreatment of normal PMN in vitro with various concentrations of C5a failed to completely deactivate PMN without affecting FMLP dependent functions. These observations demonstrate the presence of a functional defect in circulating PMN during acute cutaneous inflammation. The in vitro experiments suggest transient blocking of C5a-dependent PMN functions by a cell-bound factor which seems not to be C5a or C5adesarg.
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PMID:Transient absence of C5a-specific neutrophil function in inflammatory disorders of the skin. 316 55


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