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)

To investigate the possibility that human polymorphonuclear leukocytes (PMN) elaborate sufficient amounts of hydrogen peroxide (H2O2) and other radicals of reduced oxygen to be autotoxic and retard directed cell movement and phagocytosis, the rate of ingestion of opsonized lipopolysaccharide-paraffin oil particles and movement through Nuclepore filters were studied. Ingestion rates were increased under anaerobic conditions and in normal aerobic conditions in the presence of extracellular catalase but not superoxide dismutase (SOD) or scavengers of singlet oxygen or hydroxyl radicals. Conversely, ingestion rates were decreased when cells were exposed to H2O2 or a superoxide anion (O2-)-H2O2 generating system of xanthine-xanthine oxidase. Catalase, but not SOD, prevented the effect and also enhanced the directed movement of PMN in normal aerobic conditions. PMN from volunteers administered 1600 U/day of the membrane lipid antioxidant alpha-tocopherol were hyperphagocytic but killed Staphylococcus aureus 502A less effectively than controls, suggesting that less H2O2 was available to damage PMN or kill bacteria. H2O2-dependent stimulation of the hexose monophosphate shunt, H2O2 release from phaogytizing PMN, and fluoresceinated concanavalin A cap formation promoted by H2O2 damage to microtubules were all diminished, but the release of O2- from phagocytizing PMN was not diminished in the vitamin E group. These results support the hypothesis that directed movement and phagocytosis by PMN are attenuated by autooxidative damage to the cell membrane by endogenously derived H2O2 and that the administration in vivo of vitamin E may prevent this damage by scavenging H2O2.
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PMID:Autooxidation as a basis for altered function by polymorphonuclear leukocytes. 87 28

Previously, we have shown the close association between hepatic concentrations of N1-acetylspermidine and the radical-producing potency of several drugs. Since vitamin E, superoxide dismutase (SOD), and reduced glutathione (GSH) are known to scavenge free radicals, in this study we tested the effect of alpha-tocopherol, one of the most potent vitamin E isomers, and SOD on the lipopolysaccharide (LPS)-induced increase in hepatic concentrations of N1-acetylspermidine. The LPS-induced increase in hepatic N1-acetylspermidine was more than twice as great in vitamin E-deficient mice as in vitamin E-supplemented mice. Pretreatment with alpha-tocopherol suppressed the LPS-induced increase in hepatic N1-acetylspermidine in vitamin E-deficient mice. Alpha-tocopherol and SOD given to mice maintained on a usual diet likewise suppressed the LPS-induced increase in hepatic N1-acetylspermidine and putrescine. The hepatic concentrations of alpha-tocopherol and GSH were lower in LPS-treated mice than in control animals. Diethyldithiocarbamate, an inhibitor of SOD, and diisopropylidene (phorone), a GSH-depleting agent, enhanced the LPS-induced increase in hepatic N1-acetylspermidine. These results suggest that the LPS-induced hepatic increase in N1-acetylspermidine is connected with radical-induced injury in vivo and that superoxide anion is produced in the liver of LPS-treated mice.
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PMID:Alpha-tocopherol and superoxide dismutase suppress and diethyldithiocarbamate and phorone enhance the lipopolysaccharide-induced increase in N1-acetylspermidine concentrations in mouse liver. 164 84

The effect of alpha-tocopherol on in vitro proliferation of murine splenic lymphocyte cultures supplemented with various concentrations of the vitamin has been measured at sub-optimal, optimal and supra-optimal levels of the T-cell mitogen Concanavalin A (Con A). In the concentration range (1-25 micrograms/ml), tocopherol enhanced proliferation when administered up to 24 hours after exposure to sub-optimal and optimal concentrations of Con A; however, at supra-optimal levels of the mitogen, it appeared to inhibit proliferation. In the concentration range 50-100 micrograms/ml, tocopherol supplementation only enhanced proliferation in response to sub-optimal concentration of Con A. The spontaneous proliferation of lymphocytes in the absence of mitogens was increased by tocopherol supplementation at all concentrations tested. In contrast, there appeared to be only slight stimulation of B-cell proliferation in response to optimal concentration of bacterial lipopolysaccharide (LPS) by lower levels of vitamin E. Tocopherol supplementation of cultures over a broad range of concentrations (0.5-100 micrograms/ml) had no significant effect on cell viability before onset of proliferation at 18 hours after exposure to Con A, nor was there evidence of earlier onset of DNA synthesis in response to mitogen in the presence of 5 micrograms/ml of the vitamin. Although macrophage depletion of cultures impaired proliferation induced by Con A, tocopherol supplementation continued to stimulate proliferation at optimal and sub-optimal levels of mitogen.
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PMID:Modification of mitogen-induced proliferation of murine splenic lymphocytes by in vitro tocopherol. 177 35

Semi-chronic exposure of ICR male Mice to Aflatoxin B1 (AFB1) in non-toxic doses results in elevated lung tryptophan (TRP) levels without change in serotonin (5-HT) or 5-hydroxyindole-3-acetic acid (5-HIAA) levels. This change is organ specific in that TRP levels are not altered in spleen, duodenum, heart or central nervous system (CNS). Acute (48 hour) flunixin treatment decreases lung TRP levels and reverses the AFB1 mediated increase in lung TRP levels. On the other hand, flunixin treatment decreases CNS TRP levels in control mice but not in AFB1 treated mice. Aflatoxin B1 treated mice have an increase in splenic serotonin (5-HT) content. Acute (48 hour) treatment of mice with E. coli lipopolysaccharide (LPS) also increases splenic 5-HT, and AFB1 treatment followed by LPS have a slightly additive effect on spleen 5-HT content. Treatment of mice with LPS increases heart 5-HT, an effect which is not altered in AFB1 pretreated mice. Both LPS and AFB1 per se increases lung TYR levels although the combination of treatments is not significantly different from the control value. Flunixin treatment increases lung tyrosine (TYR) levels, an effect which is not altered by AFB1 pretreatment. Acute treatment with either LPS or flunixin decreases the CNS TRP/TYR ratio; pretreatment with AFB1 prevents those changes in the CNS TRP/TYR ratio. Central nervous system catecholamines are reduced in AFB1 pretreated mice. However, CNS catecholamine changes in AFB1 treated mice are normalized by vitamin E supplementation during the treatment period.
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PMID:Aflatoxin B1 alters central and systemic tryptophan and tyrosine metabolism: influence of immunomodulatory drugs. 190 75

Intravenous administration of soybean phosphatidylcholine liposomes containing different amounts of tocopherol acetate leads to a dose and time dependent increase of mouse liver tocopherol content, which was not observed when the preparation was given orally. When benzo[a]pyrene pretreated mice intoxicated with 400 mg/kg AAP were pretreated 2 h before with 1 g/kg phosphatidylcholine liposomes containing 4 mg/kg vitamin E acetate, these animals were protected against liver damage. Vitamin E alone or liposomes lacking vitamin E showed no protection. In an inflammatory liver disease model, i.e. fulminant hepatitis induced by intraperitoneal administration of 700 mg/kg galactosamine and 1 microgram/kg lipopolysaccharide phosphatidylcholine liposomes protected at a dose of 1 g/kg i.v. In this case, however, the protection was not due to the presence of vitamin E. These findings demonstrate the usefulness of phosphatidylcholine for liver protection and show that the protective spectrum is improved when they contain vitamin E. The data suggest that phosphatidylcholine is an excellent carrier for delivery of vitamin E to the liver.
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PMID:Hepatic uptake and antihepatotoxic properties of vitamin E and liposomes in the mouse. 236 59

Mice deficient in dietary vitamin E are impaired in their humoral and cell-mediated immunological responses. The basis for this impaired immunocompetence was investigated by using the in vitro antibody response as an assay system. Spleen cells from mice fed vitamin E-deficient diets were low responders to the antigens, sheep red blood cells (SRBC) and dinitrophenyl-L-lysine-Ficoll (DNP-Ficoll). However, they responded as well as mice fed vitamin E-supplemented diets to the relatively macrophage-independent antigen trinitrophenylated-lipopolysaccharide (TNP-LPS). This suggested that the macrophage was the cell most affected by the vitamin E deficiency. The involvement of macrophages was confirmed directly by mixing experiments, in which it was shown that macrophages from vitamin E-deficient mice were unable to support an antibody response by macrophage-depleted spleen cells from vitamin E-supplemented mice. Macrophages from vitamin E-deficient mice expressed less Ia antigen, and seemed less able to present antigen to nonadherent cells. However, it was found that macrophages from vitamin E-deficient mice not only lacked accessory cell function, but could act instead as suppressor cells. The effect of dietary vitamin E was noted with either saturated or unsaturated sources of fat in the diet.
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PMID:Adherent cell requirement for the effect of vitamin E on in vitro antibody synthesis. 661 Jul 34

The cellular sites of H2O2 formation in phagocytizing granulocytes have been identified with cerium chloride. A precipitate was visible in phagosomes and on plasma membranes from intact normal cells in the presence of either 0.71 mM NADH or NADPH. X-ray microanalysis permitted identification of cerium deposition within the phagosomes even in the absence of reduced pyridine nucleotides. Catalase ablated the formation of the reaction product. Intact granulocytes obtained from subjects receiving 1600 units of vitamin E daily for 2 weeks exhibited reaction product in the presence of NADH but not NADPH. Intact cells from subjects treated with vitamin E demonstrated diminished numbers of phagocytic vesicles containing reaction product. During phagocytosis the granulocytes treated with vitamin E consumed oxygen but exhibited significantly reduced rates of hydrogen-peroxide-dependent glucose-1-14C oxidation to 14CO2. Isolated phagocytic vesicles obtained from granulocytes after ingestion of opsonized lipopolysaccharide-paraffin oil droplets contained reaction product when exposed to 0.71 mM NADPH. No reaction product was evident at 0.71 mM NADH but was evident at 2.0 mM NADH. Isolated phagocytic vesicles from the granulocytes of subjects receiving vitamin E exhibited reaction product only in the presence of NADH. These observations suggest that vitamin E interferes with the electron transport chain apparently required for the oxidation of NADPH to form H2O2 in the phagocytizing granulocyte.
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PMID:Vitamin E--a selective inhibitor of the NADPH oxidoreductase enzyme system in human granulocytes. 661 42

The effect of vitamin E on mitogenesis by polyclonal activators was studied and the vitamin was found to be stimulatory but selective in its action. Vitamin E itself is a mitogen for murine spleen cells. At suboptimal vitamin concentrations, it was capable of stimulating the response to low levels of the thymus-dependent lymphocyte (T cell) mitogen, concanavalin A (conA), but not when conA was itself at optimal levels. When vitamin E was added to the diet at normal levels, it was not as effective in stimulating mitogenesis as it was at much higher levels. The effect of the vitamin on T cell mitogenesis could be modified by the degree of unsaturation of the dietary fat; it was more effective when dietary polyunsaturated fatty acids (PUFA) were low. Under several conditions, it was shown that vitamin E can increase the phytohemagglutinin (PHA)/conA response ratio, which may suggest an effect of the vitamin on the maturation of T cells. In normal mice, vitamin E also stimulated the response to lipopolysaccharide (LPS), a "bursa-equivalent" lymphocyte (B cell) mitogen, but it was unable to do so when spleen cells from athymic, nude mice were used. This suggests a requirement for thymic factors in order for vitamin E to stimulate mitogenesis of B cells.
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PMID:Influence of vitamin E on the mitogenic response of murine lymphoid cells. 696 30

The hypothesis was tested that vitamin E protects chickens from a lethal Escherichia coli infection by inhibiting the biosynthesis of prostaglandins, thereby activating humoral immunity and phagocytosis. When chickens were fed supplement vitamin E at the level of 300 mg/kg diet, which is six times the presently used dietary level, endogenous PGE1, PGE2, and PGF2 alpha levels decreased in the immunopoietic organs, bursa, and spleen. Antibody titers to E. coli lipopolysaccharide and phagocytosis increased at the same time. Infection slightly increased prostaglandin levels and vitamin E appeared to compensate for this increase. Aspirin, a known prostaglandin inhibitor acted synergistically with vitamin E in depressing endogenous PG levels in bursa and decreasing mortality from E. coli infection.
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PMID:Vitamin E and aspirin depress prostaglandins in protection of chickens against Escherichia coli infection. 701 Sep 85

Studies have been done to determine the optimal dosage of vitamin E. Vitamin E is generally considered to be relatively nontoxic at high dosage in spite of the fact that it is a fat-soluble vitamin. From our experiments using mice, when various dosages of all-rac-alpha-tocopherol were injected into the intraperitoneal cavity every day, 1) the body weight decreased when the dose was more than 100 IU/kg per day, and all the mice died within 3 days at 400 IU/kg per day; 2) immune responses investigated by lymphoproliferative assays with phytohemagglutinin, concanavalin A and lipopolysaccharide were enhanced significantly between 5 and 20 IU/kg per day, but were inhibited by 80 IU/kg per day. When the immunopotentiation effect of vitamin E was discernible, serum tocopherol levels were about twice the control values. From our results, the optimal dosage of vitamin E was between 5 and 20 IU/kg per day, and dosages over 80 IU/kg per day were toxic to mice. We then experimented similarly with vitamin K, which is fat soluble and possesses a quinone structure resembling vitamin E. When doses between 12.5 and 150 mg/kg per day of vitamin K were injected into the intraperitoneal cavity daily fore 14 days, increase of body weight was generally inhibited. This did not depend on the dose, and there was no definite relationship between mitogen responses and vitamin K.
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PMID:Effect of vitamin E as an immunopotentiation agent for mice at optimal dosage and its toxicity at high dosage. 708 37


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