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

A marked reduction in the number of plaque-forming cells from spleens of mice infected with Schistosoma mansoni to sheep erythrocytes (SRBC) and lipopolysaccharide from Escherichia coli was observed. This reduction coincided with the late stages of the infection and was also observed in unisexual infection with male worms. Treatment of the animals with a schistosomicidal compound (oxamniquine) almost completely abolished the immunosuppression. The suppression could be induced by administration of 60 microgramg protein from worm membrane preparations (24 h before SRBC injection), but not by egg-extract injection. When the crude membrane preparation was injected 48 h before or 0 to 24 h after the SRBC challenge, the immunosuppression was not observed. Significant reduction of footpad swelling was also noted in infected mice when injected with SRBC.
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PMID:Immunosuppression mediated by adult worms in chronic schistosomiasis mansoni. 32 99

Mice infected with Schistosoma mansoni were highly sensitive to the lethal effects of bacterial lipopolysaccharide (LPS). The hyper-reactive state of LPS coincided with the development around the parasite eggs of multiple granulomas in the liver. Elevated aspartate transaminase levels in blood and severe hypoglycaemia in LPS-challenged animals indicated extensive liver parenchymal cell damage. There was also a complete depletion of glycogen in hepatocytes of these animals. From this work and studies on other hepatitis models, it is suggested that individuals affected with granulomatous disorders may be at risk because of everyday exposure to LPS from the gut.
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PMID:Increased hepatotoxicity of bacterial lipopolysaccharide in mice infected with Schistosoma mansoni. 55 82

Interleukin 10 (IL-10) inhibits interferon gamma-induced macrophage activation for cytotoxicity against larvae of the human parasite Schistosoma mansoni by suppressing production of the toxic effector molecule nitric oxide (NO). In this study, the mechanism of IL-10 action was identified as inhibition of endogenous tumor necrosis factor alpha (TNF-alpha) production by interferon gamma-activated macrophages. TNF-alpha appears to serve as a cofactor for interferon gamma-mediated activation, since both schistosomulum killing and NO production were inhibited by anti-TNF-alpha antibody, whereas TNF-alpha alone was unable to stimulate these macrophage functions. IL-10 blocked TNF-alpha production by interferon gamma-treated macrophages at the levels of both protein and mRNA synthesis. Addition of exogenous TNF-alpha reversed IL-10-mediated suppression of macrophage cytotoxic activity as well as NO production. Likewise, addition of a macrophage-triggering agent (bacterial lipopolysaccharide or muramyl dipeptide), which induced the production of TNF-alpha, also reversed the suppressive effect of IL-10 on cytotoxic function. In contrast to IL-10, two other cytokines, IL-4 and transforming growth factor beta, which also inhibit macrophage activation for schistosomulum killing and NO production, did not substantially suppress endogenous TNF-alpha production. These results, therefore, describe a separate pathway by which macrophage microbicidal function is inhibited by the down-regulatory cytokine IL-10.
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PMID:Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation. 152 80

Sera from rabbits and rats vaccinated with highly irradiated cercariae of Schistosoma mansoni (VRabS, VRatS) were found to be of substantially higher affinity than sera from CBA mice vaccinated four times (4 X CVMS), single sex sera (SSS) or chronic infection sera (CIS). In contrast, VRabS and SSS appeared to possess the highest titres of antibody, followed by CIS and VRatS, with 4 X CVMS displaying the lowest titre. Two mouse strains selectively bred for high-affinity (HA) or low-affinity (LA) antibody following vaccination were tested for their ability to resist a challenge infection. LA mice, which produce high titres of low-affinity antibody, manifested significantly more resistance than HA mice, which produce low titres of high-affinity antibody. Immunoprecipitation studies demonstrated that sera from vaccinated LA mice (LVMS) recognized 125I-labelled schistosomular surface antigens more intensely than sera from vaccinated HA mice (HVMS). However, peritoneal macrophages from HA and LA mice in the presence of HVMS, LVMS or 4 X CVMS, and naive macrophages activated in vitro with interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS) mediated comparable levels of schistosomula killing in vitro. The experiments described here provide evidence that the titre of antibody rather than its affinity may be a more critical factor in the development of optimal immunity to S. mansoni.
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PMID:The role of antibody affinity and titre in immunity to Schistosoma mansoni following vaccination with highly irradiated cercariae. 210 83

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

Three groups of C57BL/6J female mice were infected with female Schistosoma mansoni cercariae alone, male cercariae alone, or both sexes of cercariae. In a longitudinal study, the spleen cell proliferative responses to the mitogens phytohaemagglutinin (PHA) and Escherichia coli lipopolysaccharide (LPS) were monitored. Significant immune suppression was found in the three infected groups when compared with uninfected controls. Within the infected groups, mice inoculated with both sexes of cercariae were significantly more suppressed than those with single-sex cercarial infection. Thus, in addition to schistosome eggs, either sex of S. mansoni worms is capable, although to a lesser extent, of inducing hyporesponsiveness of cell-mediated immunity (CMI) in chronic schistosomiasis mansoni.
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PMID:Modulation of cell-mediated immunity in mice with chronic unisexual or bisexual Schistosoma mansoni cercarial infection. 251 65

This study addresses macrophage activation in guinea-pigs vaccinated with radiation-attenuated cercariae of Schistosoma mansoni. Peritoneal exudate macrophages elicited in vaccinated animals by mineral oil injection were activated to kill larval schistosomes in vitro. Killing efficiency is dependent upon the cell: target ratio employed and is enhanced by, but is not strictly dependent on, the presence of specific antibodies. Macrophages co-cultured with parasites release superoxide radicals and hydrogen peroxide, but the use of inhibitors has shown that neither of these reactive oxygen intermediates are the causal agents of cellular cytotoxicity in this system. Oil-elicited macrophages from naive guinea-pigs do not show comparable activation; they can, however, be activated in vitro by incubation with culture supernatant fluids from schistosome antigen-stimulated spleen, or lymph node cells harvested from vaccinated guinea-pigs. Naive macrophages activated in this way kill schistosomula in vitro and release the activation markers IL-1 and superoxide anion. The macrophage-activating factor (MAF) present in spleen cell culture supernatant fluids has a MW of 35,000-55,000, but does not have the chemical characteristics of gamma-interferon. In this study MAF is shown to be released by a population of lymph node cells that does not adhere to nylon-wool columns, that responds well in proliferation assays to schistosome antigens and to the T-cell mitogen concanavalin A, but does not respond to the B-cell mitogen lipopolysaccharide. These cells have been identified as small lymphocytes.
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PMID:Immunity to Schistosoma mansoni in guinea-pigs vaccinated with radiation-attenuated cercariae. T-cell activation of macrophages for larval killing. 283 8

Monocytes from moderately eosinophilic individuals secrete material that enhances the cytotoxic activity of eosinophils against antibody-coated schistosomula of Schistosoma mansoni. This material is not a single substance, but can be fractionated into several active components of different size and different charge. Gel filtration of mononuclear cell supernatants separated the eosinophil-activating activity into a major component of molecular mass of 40 kDa and a minor component of molecular mass of less than 10 kDa. The major component exhibited further heterogeneity on fractionation by high performance liquid chromatography. The bulk of the eosinophil-activating activity could be separated from both colony-stimulating factor (CSF) alpha activity and from tumor necrosis factor (TNF) activity. However, human recombinant CSF alpha (GM-CSF), human recombinant TNF and rabbit tumor necrosis serum all had eosinophil-activating activity when tested against schistosomula. Eosinophils were not activated by interleukin 1, interleukin 2, interferon-alpha, lipopolysaccharide or phorbol myristate acetate.
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PMID:A comparison of eosinophil-activating factor (EAF) with other monokines and lymphokines. 348 22

A factor produced by lipopolysaccharide-stimulated human monocytes, monocyte-derived eosinophil cytotoxicity-enhancing factor (M-ECEF), increases the ability of human eosinophils to kill larvae of Schistosoma mansoni. In order to purify this monokine, a continuous cell line was sought as a generator of source material. It was found that high titers of an ECEF-like activity could be obtained from the U937 cell line cultured in serum-free medium. Production of this activity was optimal when cells were cultured with PMA for 2 days and were further treated with LPS for 2 days. PMA and LPS alone did not enhance eosinophil cytotoxicity and could be separated completely from U937-ECEF activity by reversed-phase HPLC. Thus, the activity was not due to carry-over of these two stimuli. U937-ECEF was compared with M-ECEF by a number of analytical methods. ECEF from both sources was resistant to several denaturing treatments but was sensitive to proteases or to reduction and alkylation. U937-ECEF exhibited activity profiles similar, if not identical, to those of M-ECEF when subjected to molecular sizing HPLC in the presence of 8 M urea, isoelectric focusing, and reversed-phase HPLC. The activity has apparent m.w. of 17,000 and 32,000, isoelectric points ranging from 3.8 to 5.1, and one or more reversed-phase HPLC retention times, depending on the method of sample preparation. These results demonstrate certain physical characteristics of M-ECEF, show that the U937 cell line is an appropriate source for the purification of M-ECEF, and provide information that will allow the design of a purification strategy. Although it appears that tumor necrosis factor (TNF) or a TNF-like molecule is a component of M-ECEF, a major component of M-ECEF is different from TNF as judged by the 1) physical characteristics of M-ECEF, 2) low direct toxicity of M-ECEF to L929 cells, 3) comparative stability of M-ECEF to heat treatment, and 4) inability of an anti-TNF monoclonal antibody to remove M-ECEF activity.
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PMID:Characterization of a factor from the U937 cell line that enhances the toxicity of human eosinophils to Schistosoma mansoni larvae. 349 78

Splenic lymphocyte blastogenic responses to mitogens and antigens were compared in Schistosoma mansoni-infected C57BL/6 and CBA mice. At 1 and 2 weeks of infection, elevated responses to phytohemagglutinin (PHA) were noted in C57BL/6, but not in CBA cultures. During the same period, elevated responses to lipopolysaccharide were observed in cultures from CBA, but not from C57BL/6 mice. Responses to both mitogens were depressed in both strains later in infection. The magnitude of antigen-specific responses was greater in CBA than in C57BL/6 cultures. A cercarial extract (CE) induced significant suppressor cell activity in normal C57BL/6 cell cultures as assessed by inhibition of syngeneic cell responsiveness to PHA. CE did not induce suppressive activity in CBA cultures. CE-induced suppression was unaffected by adherent cell removal, but was sensitive to anti-Thy 1.2 plus complement treatment. CE also directly inhibited PHA-stimulated C57BL/6 cell cultures, but enhanced cultures of CBA mice. The significance of these findings is discussed in relation to the relative strain differences seen in antigen-specific lymphocyte proliferation and the levels of protection induced after immunization with irradiated cercariae.
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PMID:Strain differences in lymphocyte responses and in vitro suppressor cell induction between Schistosoma mansoni-infected C57BL/6 and CBA mice. 616 23


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