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)

Human monocytes obtained from healthy volunteers and isolated by centrifugal elutriation were not cytotoxic to allogeneic tumorigenic cells. These freshly isolated monocytes were rendered tumoricidal following interaction in vitro for 24 hours with greater than 0.01 micrograms lipopolysaccharide (LPS)/ml or over 1 microgram nor-muramyl dipeptide/ml. Monocytes activated by this procedure produced a soluble factor that lysed tumor cells. Full expression of tumor cell lysis required a minimum of 18 hours' exposure of tumor cells to the factor. The degree of tumor cytotoxic factor (TCF) production was closely related to the intensity of monocyte activation to become tumoricidal. Significant production of TCF by monocytes was detected in the supernatants after treatment for 3 hours with LPS. TCF was also released by activated monocytes when cocultivated with tumorigenic cells. Similarly, the level of TCF production correlated with the monocyte density. TCF destroyed human allogeneic tumor cell lines (melanoma, glioblastoma, colon carcinoma, prostatic carcinoma, and breast carcinoma), but it did not affect nontumorigenic cell lines (lung and skin fibroblasts). TCF activity was not blocked by superoxide dismutase, catalase, or protease inhibitors; it was destroyed by being heated at 100 degrees C for 2 minutes. The ability of activated monocytes to release TCF could enhance host defense against cancer.
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PMID:Kinetics and function of tumor cytotoxic factor(s) produced by human blood monocytes activated to the tumoricidal state. 385 62

Neutrophil granulocytes are most active producers of potentially toxic free oxygen radicals. Since other functions of granulocytes can be affected by lymphokines or monokines, we investigated whether granulocyte oxygenation activity can also be influenced by such cellular mediators. Human granulocytes emitted strong chemiluminescence after addition of culture supernatants from human mononuclear cells stimulated with bacterial lipopolysaccharide (LPS). Response of the granulocytes was dose-dependent and was inhibited up to 90% or more by superoxide dismutase. This granulocyte chemiluminescence inducer-activity (GCI-activity) in the LPS-induced supernatants was heat-labile and sensitive to trypsin treatment. Addition of cycloheximide to the cultures inhibited the generation of GCI-activity by 80%. On HPLC gel filtration GCI-activity eluted with two distinct peaks corresponding to molecular weights of 60 +/- 10 KDa and between 1 and 5 KDa. Murine interleukin 1, human recombinant interferon-alpha and -gamma were devoid of GCI-activity. When mononuclear cells were fractionated by plastic adherence or counterflow elutriation, monocytes appeared to be the source of GCI-activity. Therefore, it appears that granulocyte oxygenation activity can be enhanced strongly by a cellular mediator derived from monocytes. This interaction of monocytes and granulocytes may constitute a new and potent pathway of phagocyte-dependent production of highly reactive and potentially toxic oxygen radicals.
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PMID:Induction of granulocyte chemiluminescence by a mediator derived from human monocytes. 394 6

We studied the effects of superoxide dismutase (SOD), an enzyme that converts superoxide into peroxide, on the cardiopulmonary response to endotoxin in sheep. Sheep (n = 18) were prepared for chronic measurement of cardiopulmonary variables, including lung lymph flow, by surgically implanting catheters under halothane anesthesia. Nine of the animals were studied before and after the administration of endotoxin (0.75 microgram/kg) with and without SOD. An additional nine animals received SOD without the lipopolysaccharide. Endotoxin produced an increase in lung lymph flow that was initially associated with a marked pulmonary arterial (PA) hypertension and reduced lymph-to-plasma protein ratio (L/P). The lymph flow remained elevated later in the response, but there was only a mild increase in PA pressure, and the L/P was normal. There was also a fall in blood neutrophils and in cardiac index. SOD increased this secondary elevation in lung lymph flow, and the corresponding L/P was greater than the preendotoxin value. The fall in neutrophil count, cardiac output, and the elevation in PA pressure seen with endotoxin were not affected by SOD. When administered in the absence of endotoxin, SOD produced no perceptible change in the cardiopulmonary and lymph values. We conclude that peroxide, hydroxyl ion, and/or other free radicals formed by the action of SOD must be responsible for a portion of the endotoxin response rather than superoxide itself.
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PMID:Potentiation of lung vascular response to endotoxin by superoxide dismutase. 398 Mar 70

Radioimmunoassays for both human copper-zinc and manganous superoxide dismutases (Cu-Zn SOD and Mn SOD, respectively) have been developed, validated, and utilized to measure the concentrations of these enzymes in cultured monocytes. Monocyte Mn SOD increased 4.7-fold over basal during 3 days of culture, an increase that was markedly enhanced by stimulation with bacterial lipopolysaccharide (LPS). Cu-Zn SOD showed a transient decrease over the culture period but was unaffected by LPS. Stimulation with muramyl dipeptide had minimal effect on Mn SOD and no effect on Cu-Zn SOD during culture, even at a concentration capable of activating the monocytes, as defined by zymosan-induced superoxide production.
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PMID:Selective induction of manganous superoxide dismutase in human monocytes. 406 26

Mice treated with Escherichia coli endotoxin (500 micrograms/kg i.p.) 24 and 1 hr before paraquat dichloride (50 mg/kg i.p.) had a 2-fold increase in 7-day cumulative mortality compared to those injected with buffered saline before paraquat. The duration of the prior exposure time to endotoxin appears to be an important determinant of the potentiating effect as more mice died after 24 than 1 hr pretreatment. The potentiating effect of endotoxin on paraquat-induced lethality is not due to increased uptake of the toxicant. Lung values of radioactivity from [14C]paraquat were not significantly different between endotoxin and buffered saline-treated mice. Despite the potentiating effect of endotoxin on paraquat-induced lethality, it appears that the lipopolysaccharide is able to provide some protection to the pulmonary capillary endothelium because pretreatment reverses an increase in serum angiotensin converting enzyme. Although not addressed in the present investigation, possible mechanisms for the potentiating effect of endotoxin on paraquat-induced lethality may involve superoxide anion generation, superoxide dismutase inhibition or both.
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PMID:Potentiation of paraquat lethality in mice by bacterial lipopolysaccharide pretreatment. 608 82

Current evidence suggests that bleomycin toxicity may be attributable to its DNA degradative activity possibly via generation of free radicals and O2 metabolites as mediators. Since lipopolysaccharide (LPS) has been known to provide protection against O2 toxicity, which is correlated with increased activity of O2 metabolite-detoxifying enzymes, the effect of this agent on bleomycin-induced pulmonary fibrosis was examined. Endotracheal bleomycin administration caused increased lung collagen synthesis. A single intraperitoneal injection of LPS (500 micrograms/kg) at day zero significantly decreased these increases. Total bleomycin-induced lung collagen increase was also significantly reduced. LPS alone had no significant effect on total lung catalase activity. Glutathiione peroxidase activity, however, was significantly decreased by 15.8% compared to untreated animals at 2 days after LPS treatment and remained unchanged at other time points. In addition, superoxide dismutase activity was significantly elevated by 30% above untreated animals only at 14 days after LPS administration and remained unchanged at other time points. Endotracheal bleomycin administration alone caused significant reductions in catalase activity at 2 days and 2 weeks after treatment, whereas glutathione peroxidase activity increased above control untreated animals at 2 and 4 weeks, respectively. Superoxide dismutase activity was unaffected by bleomycin treatment. Pretreatment with LPS before bleomycin prevented these reductions or caused increases in the activities of these enzymes at 2 days. Glutathione peroxidase was increased and was significantly greater than those animals treated with bleomycin alone. Catalase also was higher in the LPS plus bleomycin group (by 22.2%, p less than 0.05) than the bleomycin group alone. Compared to the effects on lung collagen synthesis and content, LPS treatment resulted in much less dramatic changes in total lung antioxidant enzyme activities. This discrepancy between the intensity of LPS effects on lung O2 metabolite-detoxifying enzymes and that on pulmonary fibrosis implies that the LPS-ameliorating effect on pulmonary fibrosis could not be totally explained by increased ability to detoxify O2 metabolites. Rather, the data would favor the possibility that LPS inhibits bleomycin-induced pulmonary fibrosis either by its known immunosuppressive effects or some other unknown mechanism. The former would be in agreement with previous data which suggest that an intact immune response is necessary for complete expression of the fibrogenic response to bleomycin.
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PMID:Inhibition of bleomycin-induced pulmonary fibrosis by lipopolysaccharide. 620 76

When human alveolar macrophages (AM) lavaged from healthy donors were incubated in medium with or without lipopolysaccharide (LPS) or muramyl dipeptide, they released a factor(s) responsible for tumor cell killing. The activity of the tumor cytolytic factor(s), called TCF, was determined by radioactive release assay. Human AM released variable amounts of TCF into the culture medium without any stimulation, but the release was stimulated significantly by LPS (0.1 micrograms/ml) or muramyl dipeptide (1 micrograms/ml). Maximal production of TCF by the AM was detected in the supernatant after treatment for 3 hr with LPS, and the extent of TCF release correlated with the density of AM. In cultures with LPS, the ability of activated AM to secrete TCF was maintained for 48 hr but was lost by 96 hr. After its loss, the ability to produce TCF could be restored by a second treatment with LPS. Full expression of lysis by TCF to lyse tumor cells required its interaction with tumor cells for at least 24 hr. TCF destroyed human allogeneic tumor cell lines but did not affect nonneoplastic cell lines. TCF activity was resistant to treatment with protease inhibitors, superoxide dismutase, or catalase and to heating at 70 degrees for 1 hr, but it was labile on heating at 100 degrees for 10 min. The tumoricidal activity in the supernatant of activated human AM indicates a potential effector mechanism by which AM kill neoplastic cells.
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PMID:Production of a tumor cytolytic factor(s) by activated human alveolar macrophages and its action. 669 69

A broad spectrum of agents known to block various steps in the lipid peroxidation process were tested for their ability to protect mouse spleen cells and thereby enhance their activities, in vitro, in either the primary antibody response or the lipopolysaccharide-stimulated proliferation response. Each agent (superoxide dismutase, butylated hydroxyanisole/butylated hydroxytoluene/n-propyl gallate, lucigenin, and alpha-tocopherol) was able to enhance the cellular response in both assay systems. The degree of enhancement of these immune functions was in proportion to the efficacy of each agent in blocking the overall process in lipid peroxidation. Previous work in this laboratory has shown that the enhancement of the primary antibody response by 2-mercaptoethanol (2-ME) is mediated by the enhanced availability of reduced glutathione in the culture medium. Suboptimal doses of each lipid antioxidant agent were able to enhance the antibody response in the additive manner with a suboptimal dose of 2-ME up to a maximum response equal to that achieved with an optimal dose of 2-ME alone. These data support the hypothesis that the enhancement of cellular responses in the presence of 2-ME is mediated by the lipid antioxidant activity of reduced glutathione.
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PMID:Agents which block membrane lipid peroxidation enhance mouse spleen cell immune activities in vitro: relationship to the enhancing activity of 2-mercaptoethanol. 726 79

The mechanisms by which macrophages kill ingested microorganisms were explored using Candida albicans and Candida parapsilosis. The results indicate that efficient macrophage candidacidal activity depends upon the generation of oxygen metabolites by the phagocytic cell: (a) peritoneal macrophages from mice infected with bacillus Calmette-Guerin (BCG) or injected intraperitoneally with lipopolysaccharide (LPS) released more superoxide anion (0(2)(-)) during phagocytosis of candida and killed candida better than did resident macrophages; (b) cells of the macrophage-like line J774.1, which released negligible amounts of O(2)(-), could ingest the candida normally but not kill them; (c) killing of candida by resident, LPS- elicited, and BCG-activated macrophages was inhibited by agents that scavenge O(2)(-), hydrogen peroxide (H(2)0(2)), hydroxyl radical (x OH), and singlet oxygen; and (d) all three macrophage types killed C. parapsilosis more effectively than C. albicans, and (7. parapsilosis stimulated a more prompt and vigorous burst of macrophage oxygen consumption and 0(2)(-) release than did C. albicans. Macrophages ingested C. parapsilosis slightly more quickly than C. albicans, but phagocytosis of both strains was equivalent by 60 min of incubation. Although C. albicans contained higher concentrations of the oxygen-metabolite scavengers superoxide dismutase and catalase, neither fungal species scavenged 0(2)(-) or H(2)0(2) effectively; and C. albicans was killed more easily than C. parapsilosis by a xanthine oxidase system that generates primarily H(2)O(2) at pH 7, or 0(2)(-) and x OH at pH 10. Thus, the decreased killing of C. albicans appears to result primarily from the capability of this species to elicit less vigorous stimulation of macrophage oxidative metabolism. This capability may have general relevance to the pathogenicity of microorganisms.
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PMID:Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages. 740 Jul 57

Reactive oxygen metabolites are believed to be important mediators of sepsis- or lipopolysaccharide (LPS)-induced adult respiratory distress syndrome. EUK-8 is a novel, synthetic, low-molecular-weight salen-manganese complex that exhibits both superoxide dismutase and catalase activities in vitro. We hypothesized that treatment with EUK-8 would ameliorate pulmonary dysfunction in a porcine model of LPS-induced adult respiratory distress syndrome. At T = -18 h, pigs received an intravenous priming dose of LPS (20 micrograms/kg). Anesthetized ventilated swine were randomized to receive 1) no further treatment (n = 5); 2) LPS (250 micrograms/kg from T = 0 to 60 min, n = 6); 3) LPS and a low dose of EUK-8 (10-mg/kg bolus at T = -15 min and 1 mg/kg.h from T = 0 to 240 min, n = 6) or 4) LPS and a higher dose of EUK-8 (10-mg/kg bolus and 3 mg/kg.h, n = 6). Treatment with EUK-8, particularly at the higher dose, significantly attenuated many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance and pulmonary edema. LPS caused an increase in lung tissue malondialdehyde content that was abrogated in both EUK-8-treated groups. EUK-8 treatment had no effect on circulating plasma levels of tumor necrosis factor-alpha, thromboxane B2 or 6-keto-prostaglandin F1 alpha. We conclude that EUK-8 prevents many of the manifestations of LPS-induced adult respiratory distress syndrome in pigs by detoxifying reactive oxygen metabolites without affecting the release of other important proinflammatory mediators.
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PMID:EUK-8, a synthetic superoxide dismutase and catalase mimetic, ameliorates acute lung injury in endotoxemic swine. 747 69


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