Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat serosal mast cells (MCs, 85-90% pure), obtained from peritoneal washing of Wistar albino rats, produced a significant amount of superoxide anions (O2.-) as measured by the increase in absorbance due to the reduction of ferricytochrome c; they were also able to generate a nitric oxide (NO)-like factor, as measured by two bioassay systems: i) inhibition of platelet aggregation and ii) stimulation of MCs guanylate cyclase. Incubation of MCs with human washed platelets resulted in an inhibition of thrombin-induced platelet aggregation which was proportional to cell number. The inhibitory activity of MCs was potentiated by substances which preserve NO (superoxide dismutase, SOD), and reversed by compounds which inactivate NO (oxyhaemoglobin, oxyHb) or which inhibit its synthesis (NG-monomethyl-L-arginine, MeArg). Mechanical stimulation of MCs produced a time-dependent increase in the levels of their cGMP but not cAMP; this increase was enhanced by E. coli lipopolysaccharide (LPS). NO generators such as sodium nitroprusside (NaNp) also augmented the levels of cGMP in MCs. NaNp inhibited in a dose-dependent manner the release of histamine evoked by compound 48/80 (0.5 microgram/ml), but not by the O2.--generating system (xanthine-xanthine oxidase), suggesting a bidirectional regulation of histamine release afforded by O2.- and NO.
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PMID:Mast cells as a source of superoxide anions and nitric oxide-like factor: relevance to histamine release. 172 22

The effects of phorbol ester (TPA) and other known stimulators such as tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide on induction of mRNA for manganese-superoxide dismutase (Mn-SOD) were investigated in various cell lines. TPA enhanced Mn-SOD mRNA expression in TNF-resistant cell lines including HeLa cells, in which the other reagents also induced expression of the gene, but did not affect TNF-sensitive cells, in which the other stimulators did not alter expression of the gene. HeLa cells which had been desensitized to TPA by pretreatment with TPA for 24 h expressed Mn-SOD mRNA at a slightly higher level than the cells without TPA treatment. TPA-pretreated cells stimulated with TNF, however, expressed Mn-SOD mRNA at about twice the level of TNF-stimulated, TPA-untreated cells. When protein synthesis was inhibited by cycloheximide during TPA pretreatment, TNF no more enhanced the Mn-SOD mRNA accumulation. These data suggest that at least two separate signal-transducing pathways are involved in expression of this gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulation with TNF, interleukin-1, or lipopolysaccharide and in which a protein factor that can be induced by TPA treatment is involved.
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PMID:Phorbol ester induces manganese-superoxide dismutase in tumor necrosis factor-resistant cells. 174 13

Tumor necrosis factor (TNF), a macrophage product released in response to endotoxin and other stimuli, has been shown to be a central mediator of endotoxin or septic shock. However, its highly conserved and wide-ranging physiological effects suggest that it may also be an essential cytokine in the host defense against acute bacterial infection or sepsis. A single nontoxic dose of human recombinant TNF administered intravenously 24 h prior to a lethal infusion of Escherichia coli lipopolysaccharide (LPS) completely prevented acute LPS-induced hypotension, ameliorated tissue injury in the lungs and liver, and improved survival in male Fisher 344 rats. The protective effects of TNF were dose dependent and required a 24-h pretreatment interval. After the infusion of LPS, animals in both groups (TNF-treated animals and saline-pretreated controls) initially appeared acutely ill and had a similar severe metabolic acidosis, indicating that TNF did not inactivate or prevent the toxic effects of LPS. Twelve hours after the administration of TNF, the gene for manganous superoxide dismutase, a mitochondrial enzyme which scavenges toxic reactive oxygen species and is induced during conditions which generate a free radical stress, was expressed in liver tissue, suggesting that the induction of manganous superoxide dismutase may be an important in vivo protective mechanism against cellular injury during lethal endotoxemia.
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PMID:Single-dose tumor necrosis factor protection against endotoxin-induced shock and tissue injury in rats. 193 48

Bacterial lipopolysaccharide (LPS) was shown to produce an induction of manganese superoxide dismutase (Mn SOD) mRNA levels in porcine pulmonary artery endothelial cells (PAEC). Additional studies in porcine PAEC also demonstrated induction of Mn SOD mRNA in response to the inflammatory mediators interleukin 1 and tumor necrosis factor. On the other hand, we observed no change in Mn SOD mRNA within 24 h of a hyperoxic exposure. The induction of Mn SOD by LPS was blocked by both a RNA synthesis inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide. The data implicate the involvement of Mn SOD in the acute phase response of pulmonary endothelial cells.
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PMID:Regulation of manganese superoxide dismutase in porcine pulmonary artery endothelial cells. 205 89

A simple method is described to monitor the superoxide dismutase (SOD)-inhibitable production of superoxide anion (O2-.) in the liver. The isolated rat liver was perfused in situ with ferricytochrome c, and the reduction of this substrate during perfusion was determined. Within 30 s after the introduction of the substrate, significant reduction of ferricytochrome c was observed and stabilized at 2-4 min. A marked reduction of the substrate was observed in the livers of rats that received Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) in vivo 3 h before liver perfusion. Ferricytochrome c reduction was inhibited by SOD, but not significantly with allopurinol or deferoxamine mesylate in the livers of LPS-treated rats. Control livers exhibited only a small reduction of the substrate, and this was not significantly inhibited by SOD. After in vivo LPS administration, O2-. production peaked in the liver at 3 h (6.6 nmol/min) and returned toward normal at 6 h (1 nmol/min) after endotoxin. The amount of O2-. generated by the endotoxic livers was dose related. At 3 h post-LPS, neutrophil infiltration and necrotic areas were found in the histological sections of the liver with concomitant elevation of serum aminotransferases, indicating hepatic abnormalities during the early stage of endotoxemia. Phorbol myristate acetate in the perfusion system markedly enhanced O2-. generation in the endotoxic liver. These results show that the perfused rat liver can be used to measure O2-. generation following in vivo stimuli. The data also demonstrate that O2-. release after LPS treatment in vivo is a short and early event and may have an important role in hepatic injury in endotoxemic conditions.
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PMID:Superoxide anion generation by in situ perfused rat liver: effect of in vivo endotoxin. 217 53

Incubation of human washed platelets with bovine aortic endothelial cells (ECs) treated with indomethacin resulted in an inhibition of thrombin-induced platelet aggregation that was dependent on the number of ECs added. Preincubation of ECs with Escherichia coli lipopolysaccharide (LPS; 0.5-2.0 micrograms/ml) for 1 min significantly enhanced their inhibitory activity. This effect was potentiated by superoxide dismutase (60 units/ml) and reversed by oxyhemoglobin (5-10 microM), indicating that the inhibition was due to the release of endothelium-derived relaxing factor (nitric oxide). When the ECs were pretreated with NG-monomethyl-L-arginine (30-300 microM) before LPS, the antiaggregatory activity was strongly reduced. The reduction of activity by NG-monomethyl-L-arginine was reversed by L-arginine (100 microM) but not by D-arginine (100 microM). Under similar conditions, LPS also enhanced the antiaggregatory activity of ECs grown on beads. The immediate enhancement by LPS of the release of endothelium-derived relaxing factor from endothelial cells may contribute to the rapid fall in blood pressure associated with endotoxin shock in vivo.
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PMID:Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide. 218 41

Superoxide radicals and their metabolite(s) have been postulated to play an important role in the pathogenesis of inflammation. Hence, superoxide dismutase (SOD) has been used to reduce tissue injury caused by reactive oxygens. However, protection of the cornea and other ocular tissues from oxygen toxicity could not be achieved by administering SOD presumably due to its unfavorable in vivo behavior. To scavenge superoxide radicals on the outer surface of corneal epithelial cells, the authors synthesized an acylated SOD derivative (AC-SOD) by linking capric acid. When instilled into rabbit eyes, a significant amount of AC-SOD remained bound to the corneal surface for a fairly long time. Intracorneal injection of lipopolysaccharide (LPS) triggered infiltration of polymorphonuclear leukocytes (PMNs) to the cornea and induced severe keratitis. Topical administration of AC-SOD to the LPS-treated cornea markedly inhibited the infiltration of PMNs and suppressed the occurrence of keratitis. Under identical conditions, topically administered SOD was rapidly removed by tears and, hence, did not inhibit LPS-induced keratitis. When the number of PMNs in the systemic circulation was reduced by intravenous administration of hydroxyurea, LPS-induced keratitis was inhibited markedly. These results indicate that superoxide radicals and circulating PMNs might play a critical role in LPS-induced keratitis.
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PMID:Inhibition of corneal inflammation by an acylated superoxide dismutase derivative. 221 Sep 92

A series of experiments was conducted to examine the effects of the N-oxidized metabolite of procainamide, procainamide hydroxylamine (PAHA), on reactive oxygen species (ROS) production by macrophages in vitro, as well as on the release of the cytokine interleukin-1 (IL-1). Results with PAHA were compared with those from the parent compound, procainamide, and in some cases with other procainamide metabolites such as N-acetylprocainamide or nitrosoprocainamide. The effects of PAHA on ROS production by mouse and rat macrophages were complex, resulting in both stimulatory and inhibitory activity depending upon the PAHA concentration and whether macrophages were resting or elicited. The primary effect of PAHA appeared to be a stimulation of ROS production. Monocytes pretreated with PAHA (20 microM) depressed the responsiveness of lymphocytes in co-culture to a T-cell mitogen (conconavalin A) but not a B-cell mitogen (lipopolysaccharide). This effect was inhibited when monocyte pretreatment with PAHA was accompanied by the antioxidants, catalase or superoxide dismutase. IL-1 production by rat adherent splenocytes was unaffected by PAHA in concentrations that were not cytotoxic. These observations suggest that the oxidative metabolism of procainamide to PAHA may result in enhanced production of ROS by macrophages contributing its toxicity to lymphocytes.
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PMID:Effects of procainamide hydroxylamine on generation of reactive oxygen species by macrophages and production of cytokines. 229 61

Although administration of 100 mg galactosamine caused severe hepatic injury in C3H/HeN mice, splenectomy reduced the grade of this hepatotoxicity. However, this hepatic injury was scarcely detected in the endotoxin-resistant C3H/HeJ mice. In addition, in contrast to high lethality in C3H/HeN mice with a combined administration of galactosamine and endotoxin, splenectomy rendered C3H/HeN mice slightly resistant to this treatment. Further resistance was demonstrated in C3H/HeJ mice. In an attempt to clarify the role of endotoxin-responsive spleen cells in the pathogenesis of hepatic injury, we investigated galactosamine-induced hepatic injury by transfer of lipopolysaccharide-treated C3H/HeN or C3H/HeJ spleen cells. Both oxygen-derived free radical production and the proportion of macrophages in spleen cells were markedly enhanced in C3H/HeN mice after an intraperitoneal injection of lipopolysaccharide. Further increase in oxidative free radical production was found in the dish-adherent cells (macrophages). These enhancements were not demonstrated in lipopolysaccharide-treated C3H/HeJ spleen cells. Although hepatic injury was not demonstrated in both C3H/HeN and C3H/HeJ mice treated with 35 mg galactosamine alone, severe hepatotoxicity was found in these galactosamine-treated mice when they received lipopolysaccharide-activated C3H/HeN spleen cells, especially macrophages. Simultaneous administration of superoxide dismutase with the activated spleen cells reduced the grade of hepatic injury. On the other hand, hepatic injury was not demonstrated in the galactosamine-treated C3H/HeN or C3H/HeJ mice when they received lipopolysaccharide-treated C3H/HeJ spleen cells, although 3H-galactosamine incorporation into hepatocytes was nearly identical in both C3H/HeN and C3H/HeJ mice. These results suggest that oxidative free radicals of lipopolysaccharide-responsive macrophages could contribute to the pathogenesis of galactosamine-induced hepatic injury.
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PMID:Role of endotoxin-responsive macrophages in hepatic injury. 230 97

Explanted hepatic granulomas, eosinophils obtained from the peritoneal cavity of schistosome-infected mice, schistosome egg granuloma macrophages, alveolar macrophages, and activated peritoneal macrophages obtained from Listeria-infected mice were miracidicidal when cultured at 21% oxygen. This activity was markedly attenuated at physiologic oxygen concentrations (1-15%). Catalase and superoxide dismutase blocked the miracidicidal activity of inflammatory cells but did not prevent granuloma-mediated egg killing. However, the biomimetic superoxide dismutase, copper (II) [diisopropyl salicylate]2, inhibited granuloma-mediated egg killing in a dose-dependent, apparently nontoxic manner. Thioglycollate-elicited macrophages did not kill schistosome egg miracidia even when cultured in 21% oxygen, unless pretreated with lipopolysaccharide. Isolated schistosome eggs initiated an oxidative burst in macrophages, as measured by superoxide anion production. This burst was suppressed at reduced oxygen concentrations. Thus schistosome egg miracidia can be killed nonspecifically by macrophages through the release of cytotoxic reactive oxygen intermediates triggered by the egg. This activity is not supported by the oxygen concentrations found in most tissues, with the possible exception of the lung. Schistosoma mansoni eggs, injected intraveneously and lodged in the pulmonary vasculature of mice, were killed rapidly, with a half life of 3.5 days. Eggs, injected into the mesenteric veins and lodged in the liver, remained fully viable for several weeks. The data suggest that the high oxygen tension of the lung allows for the increased production of reactive oxygen intermediates (ROI) by local inflammatory cells, which in turn increases their miracidicidal efficiency. Conversely, the relatively hypoxic environment of the liver decreases ROI production by local inflammatory cells and decreases their miracidicidal efficiency.
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PMID:Physiologic oxygen tensions limit oxidant-mediated killing of schistosome eggs by inflammatory cells and isolated granulomas. 231 8


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