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)

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

The immunotoxicity of the glycol ether 2-methoxyethanol (ME) was evaluated in adult Fischer 344 rats using a variety of in vitro and in vivo immune function assays. In the first phase of this study, male rats were dosed by oral gavage with ME in water, at dosages ranging from 50 to 200 mg/kg/day, for 10 consecutive days. Decreases in thymus weights were observed at dosages of 50-200 mg/kg/day in the absence of decreased body weights. Lymphoproliferative (LP) responses to concanavalin A and phytohemagglutinin were reduced at 50-200 mg/kg/day while pokeweed mitogen and Salmonella typhimurium mitogen responses were reduced at 200 mg/kg/day. No alterations were observed in natural killer cell activity, mixed lymphocyte reaction, or cytotoxic T lymphocyte responses. The frequency of W3/25-positive splenocytes was reduced in rats dosed at 200 mg/kg/day. Interleukin-2 production was reduced in splenocytes from rats exposed to all dosages of ME. The plaque-forming cell (PFC) response to sheep red blood cells was enhanced in rats dosed at 50 mg/kg/day. However, the PFC response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was suppressed at all dosages. Similarly, the PFC response to TNP-LPS was suppressed in adult female rats dosed with ME. A reduction in the expulsion of adult worms was observed in rats dosed at 200 mg/kg/day that were infected with Trichinella spiralis. A number of male reproductive parameters were also evaluated in rats dosed with ME over 10 days. A significant reduction in testicular weight was observed in rats dosed at 200 mg/kg/day. In the second phase of this study, the PFC response to TNP-LPS was employed to assess the role that metabolism of ME to 2-methoxyacetic acid (MAA) plays in the immunotoxicity of this glycol ether. Ten-day oral dosing with MAA resulted in the inhibition of the PFC response to TNP-LPS at dosages of 50-200 mg/kg/day. Concomitant exposure of rats to ME and the alcohol dehydrogenase inhibitor 4-methylpyrazole blocked ME-induced suppression of this PFC response. Attempts to ameliorate ME-induced suppression of the PFC response with serine, which has been shown to reverse ME-induced developmental and reproductive toxicity, were unsuccessful. These results suggest that the immune system may be more sensitive than the reproductive system to the toxic effects of ME. Furthermore, it appears that MAA is the proximate toxicant for ME-induced alterations in the immune system, as has been demonstrated for ME-induced reproductive and developmental toxicity.
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PMID:Immunotoxicity of 2-methoxyethanol following oral administration in Fischer 344 rats. 185 47

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

Splenocytes from 25 patients with severe hepatosplenic schistosomiasis mansoni were obtained after therapeutic splenectomy. Spleen cells were phenotyped and analysed for responsiveness to mitogens or heterogeneous schistosome-derived antigenic preparations (eggs, SEA; adult worms, SWAP; cercariae, CERC) in blastogenesis assays and lymphokine production systems, and were compared with peripheral blood mononuclear cells (PBMN). Splenic lymphocytes were 55% T lymphocytes (sheep erythrocyte rosette-positive) and 37% surface immunoglobulin-positive B lymphocytes. The mean T4+:T8+ ratio of these splenocytes was 1.0. Phytohaemagglutinin stimulated spleen cell production of the lymphokine mitogenic factor, but exposure to SEA or SWAP did not. Spleen cell and PBMN blastogenic responses to SEA and SWAP were sometimes, but not always in accord. Removal of plastic adherent cells allowed the non-adherent spleen cells of 30-40% of the patients to respond substantially more vigorously to SEA, SWAP and CERC. Spleen cells from a subgroup of 20-30% of the patients failed to respond to the schistosomal antigens regardless of removal of adherent cells. Spleen cell responses to gram-negative lipopolysaccharide peaked on day 5 or 6 of culture, and were augmented by adherent cell removal. Pokeweek mitogen-stimulated responses were optimal on day 5 of culture. Spleen cells from most severe, hepatosplenic schistosomiasis mansoni patients do not respond well to schistosomal antigens or B-cell mitogens. The splenic responses of many of these patients were elevated by the removal of adherent spleen cells.
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PMID:Immune responses during human schistosomiasis mansoni. XIII. Immunological status of spleen cells from hospital patients with hepatosplenic disease. 309 36

Model systems to study the effects of chemicals of environmental concern on bacterial and parasitic diseases as well as the immunosurveillance and destruction of transplantable tumor cells were described and evaluated. Studies were conducted in female B6C3F1 mice following adult or pre/postnatal exposure to several prototype chemicals. The prototype chemicals employed included the synthetic estrogen diethylstilbestrol (DES), the polycyclic aromatic hydrocarbon benzo(a)pyrene (B[a]P), and the carcinogenesis promoting agent 12-0-tetradecanoyl-phorbol-13-0-acetate (TPA). The host resistance models employed depend primarily on functional thymus-dependent immunity, although humoral immunity is suggested to have a role in the parasite model as well. These models include: subcutaneous challenge with a dose of PYB6 tumor cell causing a 10-20% incidence (TD(10-20)) of tumor; intravenous challenge with B16 melanoma cells; challenge with a dose of Listeria monocytogenes causing a 10-20% incidence of mortality (LD(10-20)); challenge with a dose of E. coli lipopolysaccharide endotoxin causing a 10-20% incidence of lethality (LD(10-20)); and challenge with larvae of Trichinella spiralis for parasite expulsion kinetic studies. Increased mortality was observed following Listeria monocytogenes challenge in DES-exposed mice. B(a)P and TPA exposure did not alter host resistance to this organism. The increased mortality observed following DES was associated with a significant increase in the number of viable Listeria in the spleens and livers at 4 days, a time when T-cell immunity is thought to be expressed, but bacterial counts were similar to control mice at day 1, a time when MPhi are thought to exert their greatest effect. These data suggest that the increased Listeria susceptibility found following DES exposure may result from a T-cell defect, although the intracellular killing capacity of DES-treated Mvarphi's has not been well examined. Tumor susceptibility studies following challenge with 5 x 10(3) viable syngeneic PYB6 tumor cells revealed that nontreated adult B6C3F1 mice resisted tumor formation, with only a 10-20% incidence of tumor formation. In contrast, mice exposed to DES or TPA as adults had a tumor frequency of from 70-100% following TPA and up to 90% following DES exposure. In all cases the tumors were progressive and resulted in death. B(a)P did not alter the frequency of tumor incidence from controls in this model. Preliminary data, using the B16 melanoma intravenous challenge model and (125)IUdR to quantitate tumor mass revealed this model was sensitive to non-specifically activated macrophage kill. DES treated mice with activated macrophages did not demonstrate increased tumor mass, while mice exposed to TPA or the potent immunosuppressive agent cyclophosphamide had a significantly increased tumor mass in their lungs. Expulsion of Trichinella spiralis adults from the gut also apparently required functional T-cells and possibly some element of humoral immunity. Mice exposed to DES and B(a)P exhibited increased numbers of adult worms in the gut at day 14. Sensitivity to gram-negative endotoxin (LPS) was apparently increased following exposure to DES or B(a)P. These data suggest that the detoxification of LPS is related to an intact Mvarphi population. The data presented here demonstrate the sensitivity of the host resistance assay panel proposed for detecting immune alteration. Alteration of T-cell function appeared to correlate with increased susceptibility to bacterial and tumor cell challenge.
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PMID:Application of tumor, bacterial and parasite susceptibility assays to study immune alterations induced by environmental chemicals. 706 May 48

Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post-infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes from uninfected rats to produce free radicals in response to adult worms. The cytokines, gamma-interferon and tumour necrosis factor (TNF) can be detected in plasma during infection with a variety of organisms and several lines of immunological and pathophysiological evidence, including radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasiliensis. We therefore investigated whether gamma-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and whether the presence of these cytokines correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. However, gamma-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat gamma-interferon had no effect on the ability of plasma to prime free radical generation. TNF was detected in the plasma of heavily-infected rats but only at very low levels (< 1 ng/ml), though copius in vivo synthesis of TNF could be induced by treatment of the infected rats with lipopolysaccharide (LPS). However, neither parasite-induced nor parasite plus LPS-induced plasma TNF correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nippostrongylus brasiliensis: ability of plasma to prime free radical generation by leukocytes in response to adult worms not due to gamma-interferon or tumour necrosis factor. 788 47

The effect of Toxocara (T.) canis antigen (TcAg) on lymphocytes was studied in vitro using normal murine spleen cells and human peripheral blood lymphocytes. TcAg prepared from adult worms stimulated murine spleen cells to proliferate at concentrations of 1-125 micrograms/ml. The responder cells TcAg are B cells, because the response was depleted by the treatment of spleen cells with anti-immunoglobulin (Ig) antibody and complement and after separation on a nylon wool column. This response was not due to the contamination of lipopolysaccharide (LPS), because TcAg could stimulate C3H/HeJ spleen cells which are low responders to LPS. Not only the proliferative response but also polyclonal IgG and IgE production were stimulated with TcAg. TcAg also stimulated macrophages to produce interleukin-1 and could stimulate human B cells. These results suggest that TcAg is a potent B cell mitogen and this activity may be relevant to the alteration of immunological functions in hosts infected with T. canis.
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PMID:B cell mitogenic activity of Toxocara canis adult worm antigen. 883 60

The macrophage is a major component of the inflammatory response induced by lymphatic tissue-dwelling filariae. Intraperitoneal (i.p.) infections with Brugia pahangi in Mongolian gerbils, or jirds (Meriones unguiculatus), induce a peritoneal inflammatory response characterized by accumulation of numerous macrophages and fewer eosinophils. This inflammatory response is associated with the release of microfilariae by female worms. The aim of this study was to investigate the activation state of the peritoneal macrophages during the course of i.p. infections with either male or female worms. Activation was determined by a toxoplasmacidal assay and assays which measured the production of tumor necrosis factor (TNF)-like activity and nitric oxide (NO) production. The development of these assays with jirds was initially conducted in parallel with the mouse system, which served as a positive control. Jird macrophages became activated to kill Toxoplasma gondii by in vivo immunization with Mycobacterium bovis BCG in a pattern similar to that of mouse macrophages. However, unlike the mouse system, supernatants from purified protein derivative- or concanavalin A-stimulated jird splenocytes plus lipopolysaccharide failed to activate jird macrophages in vitro or induce NO production. These results indicate that factors involved in jird macrophage activation may differ from those demonstrated in the mouse system and other systems. i.p. infections of 15 days in duration with either male or female worms induced macrophage activation as measured by Toxoplasma killing and TNF production. These responses decreased as the infection progressed to the chronic period on a time course that parallels the down regulation of experimental B. pahangi granulomas. There was no evidence of NO production by activated jird macrophages. These data indicate that macrophage function is down modulated during filarial infection and suggest that mechanisms involved in macrophage deactivation are related to those that induce down modulation of the systemic granulomatous inflammatory response in the jird. This response is not dependent on the microfilarial stage of the parasite and is also independent of mechanisms which induce peritoneal accumulations of macrophages.
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PMID:Down regulation of macrophage activation in Brugia pahangi-infected jirds (Meriones unguiculatus). 948 96

To examine the role that lipopolysaccharide (LPS)-like molecules from the filarial intracellular endobacteria Wolbachia might play in the development of filarial infections, a natural infection in the LPS-nonresponsive C3H/HeJ mouse strain was compared to that of the LPS-responsive C3H/HeN mouse strain. C3H/HeN mice have been shown to be susceptible to the rodent filarial nematode Litomosoides sigmodontis, with the development of adult worms including females containing mature microfilariae (first stage larvae) in the uterine tubes. However, free microfilariae are not detected. In this study the worm burden and worm length were not significantly different between the C3H/HeN and C3H/HeJ mice. However, the fertility of worms from CeH/HeJ mice was found to be higher than those from C3H/HeN mice. Significantly, mature microfilariae were found at the site of infection only in C3H/HeJ mice. These results indicate a role for TLR4 signaling in the immune response that inhibits worm embryogenesis and prevents the release of microfilariae or directly kills released microfilariae.
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PMID:Involvement of Toll-like receptor 4 in the embryogenesis of the rodent filaria Litomosoides sigmodontis. 1259 64

To investigate Yersinia pathogenicity and the evolutionary divergence of the genus, the effect of pathogenic yersiniae on the model organism Caenorhabditis elegans was studied. Three strains of Yersinia pestis, including a strain lacking pMT1, caused blockage and death of C. elegans; one strain, lacking the haemin storage (hms) locus, caused no effect. Similarly, 15 strains of Yersinia enterocolitica caused no effect. Strains of Yersinia pseudotuberculosis showed different levels of pathogenicity. The majority of strains (76 %) caused no discernible effect; 5 % caused a weak infection, 9.5 % an intermediate infection, and 9.5 % a severe infection. There was no consistent relationship between serotype and severity of infection; nor was there any relationship between strains causing infection of C. elegans and those able to form a biofilm on an abiotic surface. Electron microscope and cytochemical examination of infected worms indicated that the infection phenotype is a result of biofilm formation on the head of the worm. Seven transposon mutants of Y. pseudotuberculosis strain YPIII pIB1 were completely or partially attenuated; mutated genes included genes encoding proteins involved in haemin storage and lipopolysaccharide biosynthesis. A screen of 15 defined C. elegans mutants identified four where mutation caused (complete) resistance to infection by Y. pseudotuberculosis YPIII pIB1. These mutants, srf-2, srf-3, srf-5 and the dauer pathway gene daf-1, also exhibit altered binding of lectins to the nematode surface. This suggests that biofilm formation on a biotic surface is an interactive process involving both bacterial and invertebrate control mechanisms.
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PMID:A Caenorhabditis elegans model of Yersinia infection: biofilm formation on a biotic surface. 1460 Feb 34


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