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)

Several cytokines have previously been shown to prime macrophages for enhanced release of oxygen radicals in response to subsequent stimulation. We now demonstrate that the presence of the macrophage-specific colony stimulating factor-1 (CSF-1) inhibits the priming of murine macrophages by a variety of agents including tumor necrosis factor alpha, granulocyte/macrophage colony stimulating factor, interferon-gamma, and bacterial lipopolysaccharide. CSF-1 is also able to reduce the respiratory burst in the absence of priming. Our results indicate that CSF-1 is a potent negative regulator of the macrophage respiratory burst which acts to oppose the priming (enhancing) action of macrophage activating agents. We propose that CSF-1 may have a potentially important and previously unrecognized, role as a physiological regulator which restricts or terminates the activation of macrophages in order to prevent an uncontrolled inflammatory reaction.
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PMID:Colony stimulating factor-1 is a negative regulator of the macrophage respiratory burst. 219 64

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 rat model was used to study the effects of endotoxemic shock in vivo on diaphragmatic tension generation and diaphragmatic metabolism in vitro. Animals were injected with E. coli lipopolysaccharide (30 mg/kg) and killed at fixed times after injection. The hemidiaphragms were isolated in an organ bath, and tension generation was measured during electrical stimulation of the phrenic nerve or diaphragmatic muscle. Diaphragmatic oxygen consumption was measured in vitro during rest and during in vivo stimulation. Adenosine triphosphate and glycogen concentrations were measured in vivo before the animals were killed and in vitro. Tension generation was reduced in a time-dependent fashion after endotoxin at all stimulation frequencies. Both contractile fatigue and transmission fatigue were present. Glycogen stores were reduced but not depleted. ATP concentration was reduced in vivo but recovered in vitro. Diaphragmatic oxygen consumption was reduced in vitro at rest and during stimulation. The results suggest that endotoxemic shock results in diaphragmatic fatigue in a time-dependent fashion, that impaired neural or neuromuscular transmission is present in vitro, and that impaired oxygen consumption in the shocked diaphragm is associated with reduced high-energy-phosphate stores.
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PMID:Diaphragmatic fatigue after endotoxemic shock in rats: in vitro function and metabolism. 221 69

Rat hepatic mitochondrial function, including oxidative phosphorylation, fatty acid oxidative capacity, kinetic parameters of carnitine palmitoyltransferase I (CPT I), and sensitivity of CPT I to malonyl-CoA inhibition were studied in vitro in isolated mitochondria following Escherichia coli lipopolysaccharide (LPS). The hepatic mitochondrial CPT I in LPS-treated rats showed a lower apparent maximum velocity (Vmax) for palmitoyl-CoA and Ki for malonyl-CoA without changes in apparent Km for palmitoyl-CoA. The rate of oxygen consumption or end-product formation of palmitoyl-L-carnitine and octanoate was not altered, but the rate of CPT I-dependent palmitoyl-CoA (plus L-carnitine) oxidation was reduced by LPS, when acetyl-CoA produced via beta-oxidation was directed toward citrate. When acetyl-CoA was directed to acetoacetate, the oxygen consumption rates of palmitoyl-L-carnitine and palmitoyl-CoA (plus L-carnitine) were decreased by LPS, although mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity was not altered. These results indicate that hepatic mitochondria isolated from LPS-treated rats show lower ketogenic and long-chain acyl-CoA oxidative capacity than those of fasted controls, and inhibition of ketogenesis is elicited at a site distal to CPT I in addition to reduction in CPT I activity.
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PMID:Altered hepatic mitochondrial fatty acid oxidation and ketogenesis in endotoxic rats. 222 Oct 51

Quartz but not titanium dioxide (TiO2) induced the production of reactive oxygen metabolites (ROM) by human monocyte-derived macrophages, as measured by lucigenin dependent chemiluminescence. Activation of the macrophages with BCG, bacterial lipopolysaccharide and macrophage-activating factor (MAF) caused a prominent increase of quartz-induced ROM production, MAF having the strongest effect. The activation did not affect the TiO2 responses to the same extent. Assuming that ROM have a role in the pathogenesis of silica-induced disease in man, we suggest that enhancement of quartz-induced production of ROM by activated pulmonary macrophages may at least partly explain the experimental and epidemiological data indicating that activation of the immune system during infection promotes the development of silicosis.
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PMID:Quartz-induced production of reactive oxygen metabolites by activated human monocyte-derived macrophages. 222 36

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

Rhizobium leguminosarum B556 and 8002 differ only with respect to carrying symbiotic plasmids with specificity for Pisum or Phaseolus hosts, respectively. Protease-treated samples derived from free-living cultures of both strains revealed a ladder of lipopolysaccharide (LPS-1) bands after periodate-silver staining of sodium dodecyl sulfate-polyacrylamide gels. These bands were arranged as doublets. After Western (immuno-) blotting, all LPS-1 bands reacted with monoclonal antibody JIM 21, whereas monoclonal antibody MAC 57 reacted only with the upper (slower-migrating) band and monoclonal antibody MAC 114 reacted only with the lower band of each doublet pair. Preparations obtained from bacteroids of Pisum or Phaseolus nodules showed significant differences in the size distribution and antigenicity of LPS. In bacteroids from Phaseolus sp., JIM 21 and MAC 57 each stained a ladder of LPS-1 bands on sodium dodecyl sulfate-polyacrylamide gels which corresponded in mobility to the upper band of each doublet pair seen in free-living cultures. MAC 114 did not react with the LPS from Phaseolus sp.-derived bacteroids. In bacteroids from Pisum sp., only fast-migrating (lower-molecular-weight) forms of LPS-1 could be visualized on gels, but both upper and lower bands of each doublet were still present and could be stained by the appropriate monoclonal antibody, MAC 57 or MAC 114, respectively. Similarly, bacteroids from R. leguminosarum 3841, which nodulates Pisum species, differed with respect to the structure and antigenicity of their LPS-1 from bacteroids of a related strain, B625, which nodulates Phaseolus species. Physiological factors were investigated that could account for these differences between the structures of LPS-1 from free-living cultures of B556 and 8002 and that from bacteroids. The following modifications in growth conditions each tended to reduce the expression of MAC 114 antigen and enhance the expression of MAC 57 antigen: succinate rather than glucose as the carbon source; microaerobic (2.5%, vol/vol) oxygen concentrations; and acidic (pH 5 to 6) culture medium. When all three of these conditions were combined, the LPS-1 that resulted was very similar to that in bacteroids from Pisum nodules. However, it was not possible to reproduce the LPS-1 pattern observed for bacteroids from Phaseolus nodules, which maintained a ladder of LPS bands reacting with MAC 57 antibody.
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PMID:Immunochemical analysis of lipopolysaccharides from free-living and endosymbiotic forms of Rhizobium leguminosarum. 231 3

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

The effects of dietary vitamin B-6 supplementation on the development of human malignant melanoma (M21-HPB) xenografts and on in vitro responses of leukocytes were examined. Male athymic nude mice, five weeks old, were divided into two groups of 48 each and fed 20% casein diets containing pyridoxine (PN) at 4.1 (control diet) and 61.6 mg/kg diet for 10 weeks. After four weeks of dietary treatment, 20 animals from each dietary group were injected subcutaneously with 3 x 10(7) melanoma cells. After 4, 8, and 10 weeks of dietary regimen, animals from each group were killed and blood, liver, and spleen samples were obtained. Food consumption and mouse body weights were similar between groups, and no difference was noted in tumor incidence or volume. Noninjected and tumor-bearing mice given the PN 61.6 diet generally exhibited greater oxygen radical production by phagocytic cells from blood and spleen than did animals fed the PN 4.1 diet. Spleen and blood B lymphocyte proliferation in response to lipopolysaccharide (LPS) was enhanced (10 and 30%) in the noninjected animals given the PN 61.6 diet. In addition, tumor-bearing mice fed the PN 61.6 diet had significantly greater LPS-induced spleen cell proliferation at eight weeks when compared with mice consuming the PN 4.1 diet. Despite immune enhancement, tumor incidence and progression was not modified by a high level of dietary vitamin B-6. Therefore, it is tempting to speculate that tumor inhibition by high dietary vitamin B-6 may be mediated by T lymphocyte-dependent mechanisms that are lacking in these genetically immuno-deficient mice.
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PMID:Enhancement of immune status by high levels of dietary vitamin B-6 without growth inhibition of human malignant melanoma in athymic nude mice. 236 33


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