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 investigated the pathogenesis of lung injury in sepsis (septic adult respiratory distress syndrome) by focusing on the functional changes of alveolar macrophages (AMs). Sepsis was induced in male WK rats by cecal ligation and puncture. Histological examination of the lungs from this experimental model revealed edematous change at 24 h after the surgery. The protein and endotoxin concentrations in the bronchoalveolar lavage fluid (BALF) increased with time after the surgery. The time course studies of AM function after surgery indicated that AMs from septic rats were activated by endotoxins. Specifically, this was suggested by the finding that AM adherence to and spreading on a plastic dish had increased. On stimulation, these AMs enhanced generation of superoxide anions and increased release of lysosomal enzymes, such as beta-glucuronidase. On the other hand, AMs in sepsis generated much smaller amounts of arachidonate lipoxygenase metabolites, such as leukotriene B4 (LTB4) and 12- and 5-hydroxyeicosatetraenoic acids (HETEs), on stimulation than did AMs from sham rats or untreated rats. However, the concentrations of immunoreactive LTC4 in the BALF of septic rats seemed to be higher than in untreated rats. It is suggested that the AMs of septic rats released lipoxygenase metabolites in alveoli and that these AMs could not be stimulated in vitro. These functional changes in the AMs of septic rats progressed along with the sepsis. These results implicate AMs in the development and progression of septic lung injury by releasing superoxide anions, beta-glucuronidase, and arachidonate metabolites. Furthermore, we speculate that reduced production of LTB4 by septic AMs may increase host susceptibility to severe pulmonary infection during septic ARDS.
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PMID:Characteristics of alveolar macrophages in experimental septic lung. 132 90

Stable oxidant and hypochlorous acid production in neutrophils of bronchopneumonic calves was investigated. The production of these compounds was much more intense in neutrophils of diseased calves than in the control cells. The production of stable oxidants and hypochlorous acid was restrained by free radical scavengers. Functional response of neutrophils was inhibited by cyclooxygenase products and stimulated by lipoxygenase products of the arachidonic acid cascade. Superoxide anion production is not connected with the degranulation process (beta-glucuronidase release), and the two events are under different control mechanisms.
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PMID:The involvement of polymorphonuclear leukocytes in the pathogenesis of bronchopneumonia in calves. IV. Myeloperoxidase activity. 166 53

Two phospholipase A2 (PLA2) enzymes, TMVPLA2 I and TMVPLA2 II, isolated from Trimeresurus mucrosquamatus venom (TMV) induce rat hind-paw oedema in a dose-dependent manner. This response is suppressed by pretreatment with diphenhydramine, methysergide or compound 48/80, which reduces tissue histamine content. In isolated mast cells, TMVPLA2 I and TMVPLA2 II cause concentration-, time- and calcium-dependent release of histamine and beta-glucuronidase. This effect is inhibited by disodium cromoglycate, mepacrine, nordihydroguaiaretic acid, piriprost and BW 755C, but not by aspirin or indomethacin. These observations indicate that the mast cell plays a predominant role in TMVPLA2 I- and TMVPLA2 II-induced paw oedema, and that venom PLA2 enzyme needs an intact lipoxygenase pathway to induce mast cell degranulation.
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PMID:Rat paw oedema and mast cell degranulation caused by two phospholipase A2 enzymes isolated from Trimeresurus mucrosquamatus venom. 171 67

A summarizing survey of different studies in atopic eczema involving three types of cells (platelets, neutrophils, basophils) and their mediators is given. Platelets were found to release normal amounts of serotonin upon stimulation with epinephrine, thrombin and slightly reduced amounts after aggregated IgG stimulation. Serotonin uptake by washed platelets was found to be slower in atopics than in normals. Neutrophils showed a decreased release of beta-glucuronidase to stimuli like zymosan or aggregated IgG in atopics compared to controls. This might be regarded as a contributory factor to the well-known decreased resistance to infections observed in atopic eczema. Basophils in most studies released increased amounts of histamine in the atopic population compared to controls, especially after stimulation with anti-IgE. Concomitantly to the histamine release there was a slight increase in prostaglandin E2 production both in atopics and normals, which was increased by preincubation with reduced glutathion-a coenzyme of PGE2 isomerase. Histamine release tended to occur faster in atopics. Two possible factors influencing releasability characteristics were studied, namely the cyclic nucleotide system and arachidonic acid (AA) dependent mechanisms. Leucocytes of atopics showed a decreased response of cAMP to beta-adrenergic and an increased response of cGMP to cholinergic stimulation. Significant augmentation of anti-IgE-induced histamine release was observed after cholinergic stimulation. AA metabolites obviously play a regulating role in mediator release. PGE2 inhibited histamine release to various stimuli both in atopics and in normals. Indomethacin enhanced histamine release, especially after anti-IgE stimulation in atopics, while it inhibited complement-dependent release reactions both in atopics and in normals. The exogenous inhibitors of lipoxygenase eicosatetraynoic acid (ETYA) and nordihydroguaretic acid (NDGA) inhibited histamine release equally in atopics and normals. The endogenous lipoxygenase inhibitor 15-HETE showed no inhibitory but rather a slight enhancing effect upon histamine release. It is concluded that patients with atopic eczema often exhibit altered releasability patterns to a variety of stimuli. On the basis of our findings we describe "altered releasability" as one factor of a vicious cycle between increased IgE-production, mediator secretion and T cell regulatory disturbances in the pathogenesis of atopic eczema.
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PMID:Altered releasability of vasoactive mediator secreting cells in atopic eczema. 240 33

Purified peripheral blood monocytes isolated from patients with atopic dermatitis (AD) and from nonallergic normal donors were compared for their abilities to release leukotriene C4 (LTC4), leukotriene B4 (LTB4) and beta-glucuronidase in response to challenge with aggregated immunoglobulins or anti-immunoglobulins. The relationship between mediator release and the number of monocytes that formed rosettes with immunoglobulin-coated indicator cells was examined. Patients with AD had twice as many IgA- and three times as many IgE-rosetting monocytes as normal donors (48 +/- 12% versus 27 +/- 10% and 40 +/- 15% versus 14 +/- 3%, respectively), and yet the amounts of IgA- and IgE-induced LTC4 released were similar for both groups. This apparent discrepancy did not result from a decreased capacity for arachidonate metabolism via the C5-lipoxygenase pathway, since stimulation of monocytes from patients and normal donors with the calcium ionophore A23187 induced similar amounts of LTC4 and LTB4 release (LTC4, 3.0 +/- 1.7 versus 3.0 +/- 1.0 ng/10(6) cells; LTB4, 5.3 +/- 0.7 versus 5.2 +/- 0.5 ng/10(6) cells, respectively). In addition, aggregated IgG-induced LTC4 release by monocytes of both groups was similar, concomitant with an equivalent number of IgG-rosetting cells. Determination of cytophilically bound IgG and IgE by flow cytometry demonstrated that monocytes from atopic patients had more IgG bound than monocytes from normal donors. Similar amounts of IgE were detected on most monocytes from both groups, despite the higher serum IgE levels of patients. However, approximately 3% to 8% of monocytes from atopic but not normal donors stained brightly for IgE, suggesting that relatively large amounts of cytophilic IgE were bound to a small percentage of the patients' monocytes. Challenge of monocytes with anti-IgE or anti-IgG induced release of similar amounts of LTC4 for both groups, despite the presence of more cytophilic IgG on monocytes from atopic donors. These data indicate that monocytes from patients with AD release LTC4 and LTB4 in response to challenge with aggregated IgE or anti-IgE, as well as aggregated IgG, IgA, and anti-IgG. However, under our in vitro conditions, stimulation of patients' monocytes with aggregated IgA or IgE was not associated with increased mediator release, despite higher percentages of IgA- and IgE-rosetting cells compared to normal donors.
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PMID:IgG-, IgA-, and IgE-induced release of leukotriene C4 by monocytes isolated from patients with atopic dermatitis. 284 75

Activation (defined as lysosomal enzyme secretion and generation of O(2) of rat neutrophils has been measured with the use of varying doses of soluble stimuli (phorbol myristate acetate (PMA); calcium ionophore A23187; and N-formyl-methionyl-leucyl-phenyl-alanine (FMLP] and particulate agents (immune complexes and zymosan particles). With either the calcium ionophore or the chemotactic peptide (FMLP), substantial enzyme release occurred, but the amount of O(2) produced was very small. Cytochalasin B greatly enhanced the enzyme release response to the chemotactic peptide but had little effect on neutrophil responses to other soluble stimuli. The cell response to PMA resulted in the greatest production of O(2) with significant enzyme secretion. When cell stimulation with insoluble stimuli (immune complexes or zymosan particles) was studied, significant amounts of enzyme release occurred in parallel with the generation of substantial amounts of O(2). The presence of cytochalasin B enhanced the cell responses to immune complexes but had an inhibitory effect on zymosan-induced responses. As expected, the amount of lysozyme secreted by stimulated rat neutrophils tended to exceed the amount of beta-glucuronidase released from the same cells. Neutrophil responses were investigated in the presence of drugs that were demonstrated in the rat neutrophil to inhibit either the lipoxygenase or the cyclooxygenase pathway. Inhibitors of the cyclooxygenase pathway (indomethacin, piroxicam, ibuprofen, BW755C), with few exceptions, consistently enhanced the enzyme secretion response, while effects on O(2) generation were less clear-cut but tended to be predominantly inhibitory. Drugs with inhibitory effects on the lipoxygenase pathway (nordihydroguaiaretic acid and nafazatrom) had significant inhibitory effects on both enzyme secretion as well as generation of O(2). These data suggest that activation responses (enzyme secretion and O(2) generation) of rat neutrophils may be dissociated (ie, one not always accompanying the other). Further, it appears that neutrophil activation, as defined by enzyme secretion, is enhanced by products of the lipoxygenase pathway and suppressed by products of the cyclooxygenase pathway. Generation of O(2) is not affected in such a clear-cut manner. Taken together the data suggest that enzyme release and O(2) production by activated rat neutrophils may be under separate control.
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PMID:Rat neutrophil activation and effects of lipoxygenase and cyclooxygenase inhibitors. 608 68

Perturbation of the neutrophil membrane by opsonized zymosan particles activates the cell's "respiratory burst." Associated with this activation process is the generation of highly reactive oxygen products, including superoxide, and the release of lysosomal enzymes. Membrane activation also stimulates arachidonic acid metabolism and the generation of a wide variety of products through both the lipoxygenase and cyclooxygenase pathways. In isolated human neutrophils, we have evaluated the effects inhibitors of cyclooxygenase and lipoxygenase upon opsonized zymosan stimulated chemiluminescence, superoxide generation, oxygen consumption, and beta-glucuronidase release. Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase enzyme, suppressed chemiluminescence, superoxide generation, oxygen consumption, and beta-glucuronidase release. Both indomethacin, a cyclooxygenase inhibitor, and 5,8,11,14 - eicosatetraynoic acid (ETYA) an inhibitor of both cyclooxygenase and lipoxygenase, inhibited all tested neutrophil functions. However, when compared to NDGA, indomethacin and ETYA were considerably less potent. Our observations suggest that the lipooxygenase derived metabolites play a predominant regulatory role in these neutrophil inflammatory functions.
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PMID:Regulation of the human polymorphonuclear leukocyte inflammatory response by inhibitors of arachidonic acid metabolism. 609 11

Purified mature rat peritoneal mast cells, on exposure to zymosan or latex beads, phagocytize these particles, although less efficiently than macrophages. During phagocytosis, histamine, beta-glucuronidase, and eosinophil chemotactic factor are released from mast cells in a time-, temperature- and dose-dependent fashion. Complement components, cytochalasin B (5 microgram/ml), and indomethacin (10-6M), enhanced mediator release, whereas compound BW 755C (20 microgram/ml), a cyclooxygenase and lipoxygenase inhibitor of arachidonate metabolism, totally abolished this process. Phagocytosis of mast cell thus activates intracellular mechanisms that closely resemble those observed with other phagocytic cells. These observations add a new perspective to the role of mast cells in inflammatory events.
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PMID:Release of mediators from purified rat mast cells during phagocytosis. 618 56

Changes in cytosolic free calcium [Ca2+]i and release of beta-glucuronidase in response to leukotriene B4 (LTB4) were measured in intact neutrophils loaded with the fluorescent Ca2+ indicator, quin 2. LTB4 (10(-10) M or higher) caused a rapid rise in [Ca2+]i due to influx from the extracellular medium and release from intracellular pools as well as enzyme release. PGE2 (3 microM) did not alter [Ca2+]i whereas arachidonic acid (10 microM) raised [Ca2+]i. Pretreatment of cells with the chemotactic peptide FMLP inhibited the subsequent rise of [Ca2+]i induced by LTB4. Since chemotactic peptides activate the lipoxygenase pathway of arachidonic acid metabolism, it may be speculated that endogenous LTB4 generation is involved in neutrophil activation.
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PMID:Effect of leukotriene B4, prostaglandin E2 and arachidonic acid on cytosolic-free calcium in human neutrophils. 631 89

Timegadine, a new non-acidic anti-inflammatory agent, inhibits in a concentration-dependent way the FMLP-induced release of beta-glucuronidase and lysozyme from human granulocytes. Superoxide generation and directed migration are also inhibited. As this effect on granulocytes occurs at drug concentrations inhibiting the lipoxygenase pathway of arachidonic acid metabolism, the hypothesis that these two phenomena could be related is discussed.
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PMID:In vitro inhibition of granulocyte function by timegadine, a new anti-inflammatory agent. 632 59


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