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

Acute necrotizing pancreatitis induced by infusion of bile salt into the pancreatic duct in rats is consistently associated with acute lung injury similar to the adult respiratory distress syndrome. The role of platelet-activating factor (PAF) in this pancreatitis-associated remote organ failure (lung injury) was investigated. Pulmonary tissue levels of PAF were increased gradually and reached a level of 1345 +/- 455 pg/g (6 times the control level) at 12 hours after induction of pancreatitis, whereas pancreatic PAF levels were undetectable and blood PAF remained unchanged. This local pulmonary PAF accumulation occurred at approximately the same time as the progression of lung injury. Pulmonary responses detected (i.e., eicosanoid production, leukocytic infiltration, Evan's blue extravasation, beta-glucuronidase release) were attenuated to varying degrees by treatment of rats in which pancreatitis was initiated with the PAF receptor antagonists (WEB2170 and BN52021). Rat lung lavages were examined after a 12-hour course of pancreatitis and no changes in PAF concentration, surfactant content, and phospholipase A2 (PLA2) activity were noted. Intravenous administration of PLA2 promoted pulmonary PAF production in experimental rats with pancreatitis but not in normal rats. This observation indicates that PLA2, which was determined to be elevated in plasma during pancreatitis, may be responsible for the accumulation of PAF in the lung. In conclusion, pancreatitis-associated lung injury appears to result from an endogenous inflammatory response in which PAF may play an important role.
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PMID:Role of platelet-activating factor in pancreatitis-associated acute lung injury in the rat. 156 55

In this paper we show that TNF-alpha enhances platelet activation. Experiments were performed on a human polymorphonuclear neutrophil (PMN)-platelet cooperation system in which PMN, stimulated by FMLP, release cathepsin G (Cat.G), a serine proteinase responsible for the activation of nearby platelets. Pretreatment of the mixed cell suspension with 5 ng/ml TNF-alpha resulted in a strong platelet activation (37.7 +/- 3.2% aggregation; 46.0 +/- 14.4% serotonin release) in response to a weak concentration of FMLP (1.25 x 10(-8) M) inducing by itself only 7.7 +/- 4.0% of aggregation and 3.8 +/- 4.1% of serotonin release (mean +/- SD; n = 10). This effect was concentration dependent (maximum between 5 and 10 ng/ml) and was optimal for a brief preincubation time (5 min). Under these experimental conditions the target of TNF-alpha was PMN, as shown by beta-glucuronidase release. The observed potentiation was modified neither by 0.1 mM acetyl salicylic acid (a cyclo-oxygenase inhibitor) nor by 0.1 mM BN 52021 (a platelet-activating factor antagonist), while such a phenomenon was fully inhibited by 20 micrograms/ml eglin C, a strong and specific inhibitor of the human granulocytic proteinases, elastase and Cat.G. In fact, full inhibition was also observed with 300 nM alpha-1-antichymotrypsin, a specific inhibitor of Cat.G. This clear-cut evidence of Cat.G involvement was substantiated by the enhancement of Cat.G release from FMLP-activated PMN primed with TNF-alpha. These results demonstrate that the priming of PMN by TNF-alpha may modulate the activation of other inflammatory cells, particularly of platelets. It is hypothesized that this phenomenon could contribute to pulmonary pathologies, and more specifically to the adult respiratory distress syndrome, a disease for which PMN, platelet and TNF-alpha involvement has been proposed.
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PMID:Tumor necrosis factor-alpha enhances platelet activation via cathepsin G released from neutrophils. 200 99

The usefulness of urinastatin (UST) for adult respiratory distress syndrome (ARDS) induced by gram-negative sepsis was evaluated in clinical and experimental studies. Twelve cases of clinical septic ARDS were treated with combination therapy of UST and methylprednisolone (M-PSL). Ten out of 12 responded favorably. This result was considered to some extent to be better than that of our previous experience with single administration of M-PSL for patients with septic ARDS. Pathophysiologic experiments on UST in endotoxic status were then performed. Immediately after the intravenous administration of endotoxin to rats, serum levels of beta-glucuronidase and elastase released from PMNs were increased and pulmonary edema was observed at 48-hours after the endotoxin injection. Various degrees of pulmonary edema were also observed by the intravenous administration of beta-glucuronidase and PMNs-elastase. These changes induced by the endotoxin were significantly inhibited by the intraperitoneal administration of UST, and they were inhibited more by the combination therapy of UST and M-PSL. In an in vitro study, significantly large amounts of beta-glucuronidase and elastase were released from PMNs by incubating human PMNs with endotoxin. By adding UST to this system, the release of these PMNs proteases was inhibited. These results suggested that UST neutralizes the PMNs-elastase release in the status endotoxemics, and consequently resulted in a better prognosis in cases of septic ARDS.
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PMID:[Usefulness of a protease inhibitor (urinastatin) in ARDS with infectious diseases]. 221 25

The biochemical and histopathological response of the lung following acute and repeated (subacute) exposure to nitrogen oxide (NO2) was examined. Activities of lactate dehydrogenase, beta-glucuronidase, choline kinase, and protease inhibitor were measured in murine pulmonary tissue immediately and two days following exposure. Nonenzymatic parameters, pulmonary protein content, and wet lung weight were also monitored. Immediately following acute exposure to NO2, only the nonenzymatic parameters were elevated. By two days following acute exposure, following subacute exposure; however, the nonenzymatic parameters were attenuated with respect to the enzymatic activities. The lung exhibits a dynamic response following damage by oxidants such as NO2. This response is divided into three distinct phases (exudative, proliferative, and tolerant), which can be characterized both biochemically and histopathologically.
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PMID:Phase-dependent response of the lung to NO2 irritant insult. 263 69

The appearance of the adult respiratory distress syndrome (ARDS) during the course of acute illness is believed to result, in part, from intrapulmonary neutrophil sequestration and degranulation induced by circulating inflammatory mediators. To evaluate the role of complement-neutrophil interactions in the pathogenesis of ARDS in man, 34 patients suffering from intra-abdominal sepsis (seven), multisystem trauma (15), or acute pancreatitis (12) were serially studied with regard to neutrophil migratory responses to C5a and F-Met-Leu-Phe, lysosomal content of beta-glucuronidase and lysozyme, and simultaneously obtained plasma levels of immunoreactive C3adesArg and C5adesArg. Nineteen patients developed ARDS. In these patients, plasma C3adesArg levels obtained within 72 hours of admission to the hospital were elevated to 305 +/- 35 ng/ml compared with 145 +/- 16 ng/ml for patients who did not develop ARDS (p less than 0.0005). C5adesArg levels were not elevated in either group. In vitro studies showed that neutrophils from normal persons were able to clear all of the C5a/C5adesArg generated in up to 5% zymosan-activated serum, while no clearance of C3adesArg was identified. Patient migratory responses could be divided into three groups based on their initial (less than 72 hour) samples: (1) hyperresponsive to both N = formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a, (2) specifically deactivated to C5a, and (3) deactivated to both C5a and FMLP. Patients in the latter two groups developed ARDS. Enzyme content of neutrophils from patients who developed ARDS showed a substantial fall in beta-glucuronidase and lysozyme levels. The finding of elevated plasma C3a levels and deactivation of migratory response to C5a support the contention that complement activation had occurred in these patients and that their neutrophils had been exposed to C5a/C5adesArg in vivo. The finding of nonspecific migratory dysfunction associated with lysozymal enzyme loss, a circumstance not reproducible in vitro by C5a exposure, suggests that other stimuli produced degranulation of neutrophils made hyperresponsive by prior exposure to C5a.
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PMID:Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult respiratory distress syndrome in man. 400 15

An experimental model of haemorrhagic hypotension was standardized using rabbits to investigate the shock lung syndrome over a period of 120 minutes. Acute hypovolaemia was induced by withdrawal of blood under anaesthesia to a mean arterial pressure of 30 +/- 5 mmHg within 10 minutes. The mean leucocyte counts and the release of lysosomal enzymes (acid phosphatase and beta-glucuronidase) in the blood and in lung tissue, as well as the metabolic capacities of lung tissue in terms of protein and lipid biosynthesis, were investigated at set intervals after 30, 60, 90 and 120 minutes. The results indicate a progressive decline in leucocyte numbers over 120 minutes to about 40% of the original. An immediate granulocytopenia was observed with a relative lymphocytosis within 30 minutes. The beta-glucuronidase and acid phosphatase contents of the plasma increased with time; beta-glucuronidase activity increased progressively as leucocytes disappeared from the circulation. Concomitantly, the capacity of the lung tissue to synthesize protein and lipids was retarded with time, becoming significantly lower than baseline values after 60 minutes of hypovolaemia. The decline in leucocyte numbers in the circulation correlated well with the increase in beta-glucuronidase activity and the retarded metabolic capacity of the lung tissue.
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PMID:Shock lung--experimental studies on a haemorrhagic hypovolaemic rabbit model. 661 40

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