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)

The effect of endotoxin or lipopolysaccharide (LPS) on tolerance induction in bone marrow-derived lymphoid cells (B cells) was investigated. Dinitrophenylated amino acid copolymer-L-(glutamic acid, lysine) (DNP-GL) acts as a potent tolerogen on normal and DNP-primed B cells. LPS significantly enhanced the anti-sheep red blood cell plaque-forming cell (anti-SRBC PFC) response that occurred after the immunization with a low dose of SRBC. LPS did not induce the primary anti-DNP PFC response after the injection of DNP-GL, nor did it prevent the tolerance induction in normal and DNP-primed B cells that occured after the administration of DNP-GL.
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PMID:Ineffectiveness of lipopolysaccharide for preventing the tolerance induction in bone marrow-derived lymphoid cells with dinitrophenyl-poly-L-(glutamic acid, lysine). 79 34

Spleen cells from C3H/HeJ mice fail to respond with polyclonal antibody synthesis to mitogenic concentrations of lipopolysaccharide (LPS) which are optimal for activating spleen cells from a high-responder strain (B10.5M). This unresponsiveness is selective for LPS, since C3H/HeJ cells respond as normals to another B-cell mitogen, purified protein derivative of tuberculin. Spleen cells from low-responder mice also fail to mount a specific anti-NNP plaque-forming cell (PFC) response, when challenged in vitro by NNP-LPS. However, C3H/HeJ cells develop normal responses to another thymus-independent hapten conjugate, DNP-AECM-Ficoll. C3H/HeJ mice fail to mount a specific anti-LPS antibody response, when challenged in vivo with doses of soluble LPS which are fully immunogenic for the high-responder strain. However, C3H/HeJ mice develop normal direct and indirect PFC responses to LPS, when challenged with a thymus-dependent form of the immunogen. These results are interpreted as indicating as absolute requirement for functional mitogenicity of the antigen, in the induction of specific thymus-independent antibody responses.
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PMID:Genetical control of B-cell responses. III. Requirement for functional mitogenicity of the antigen in thymus-independent specific responses. 109 88

It is established that 2,4 DNP effect produces no changes in the total activity of lactate dehydrogenase (LDH, EC 1.1.2.3) in the heart, liver and blood serum of guinea pigs. Under the effect of lipopolysaccharide obyained from Bact. alkaligenes faecalis it increases in the liver and heart. A change in the isoenzymic spectrum is characterized bt a decrease in the LDA3, LDH4, LDH5 activity in the blood serum, an increase in the activity LDH1, LDH2 and a decrease in the LDH4, LDH5 in the myocardium, disappearance of LDH, in the liver under the effect of bacterial lipopolysaccharide. Under the effect of 2.4 DNP the activity of LDH3 in the liver increases and that of LDH3 DECREASES.
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PMID:[Effect of pyrogenes on the activity and isoenzyne spectrum of lactate dehydrogenase in tissues and blood serum of guinea pigs]. 123 40

Recent studies have demonstrated that macrophages are the cell types capable of metabolizing benzo[a]pyrene (B(a)P) within the spleens of untreated mice. Since repeated exposure to B(a)P results in immunosuppression and B(a)P is known to induce cytochrome P450 levels, the first objective of this study was to investigate whether exposure of mice to B(a)P could increase the amounts of immunosuppressive B(a)P metabolites generated and/or alter the pattern of B(a)P metabolites formed by several different splenic cell types. Mice were dosed with a daily sc dose of 200 mg/kg B(a)P or vehicle for 4 days. Separation of splenocytes based on density by centrifugation through discontinuous Percoll gradients along with immunomagnetic negative selection or antibody-mediated complement lysis was used to obtain different splenic cell populations. Cells were incubated with [3H]B(a)P for 24 hr. High-pressure liquid chromatography was used to separate and quantitate B(a)P metabolites. Results indicate that splenic macrophages of B(a)P-treated mice produced significantly greater amounts of some metabolites compared to those of vehicle-treated mice. The three major metabolites produced were an unidentified peak of polar metabolites containing polyhydroxylated metabolites, B(a)P-9,10- and B(a)P-7,8-dihydrodiols. Other splenic cell types examined did not produce metabolite amounts significantly above (T-cells, PMNs, or the capsule) or just above (B-cells) background. The second objective was to investigate the splenic cell type(s) targeted by B(a)P resulting in suppression of humoral immunity. Separation-reconstitution studies along with in vitro sensitization techniques with several different antigens (sheep red blood cells (SRBC), dinitrophenyl-Ficoll (DNP-Ficoll), lipopolysaccharide (LPS)) were used to identify splenic target cells following exposure of mice to B(a)P (200 mg/kg/day, sc for 4 days). Findings indicate that in vitro plaque-forming cell (PFC) suppression was due to alterations in the adherent (macrophage) cell population. Exposure also suppressed the PFC response to the T-dependent antigen SRBC and the T-independent antigen DNP-Ficoll, but did not suppress the PFC response to the polyclonal antigen, LPS. These data suggest that B(a)P is targeting macrophages.
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PMID:Evaluation of murine splenic cell type metabolism of benzo[a]pyrene and functionality in vitro following repeated in vivo exposure to benzo[a]pyrene. 141 70

In vitro studies were performed to determine the role of metabolic bioactivation in mediating immunosuppression by CCl4. Direct addition of CCl4 to naive spleen cell cultures sensitized with either sheep erythrocytes, DNP-Ficoll or lipopolysaccharide (LPS) resulted in a marked inhibition of the antibody forming cell (AFC) response to all three of the selected antigens at 3.0 mM concentration in culture. However, this inhibition was primarily due to the direct cytotoxic effects of CCl4 on spleen cells following 3-5 days of culture in the presence of the chemical as evidenced by a decrease in cell number and viability and by the absence of selective effects on T-cell dependent humoral responses which is contradictory to the effects observed in vivo. Co-incubation of splenocytes for 1 h with primary hepatocytes, but not with subcellular metabolic activation systems, such as S9 or microsomes, enhanced the immunotoxic effects of CCl4 in vitro. Interestingly, a 3-h co-incubation of spleen cells with metabolically active hepatocytes in primary culture resulted in an even greater potentiation of the immunotoxic effects of CCl4 as determined by the T-cell dependent IgM AFC response. Conversely, under identical conditions, CCl4 did not suppress humoral responses to the polyclonal B-cell activator LPS which is in agreement with the effects produced by in vivo exposure to CCl4. It is important to emphasize that for the metabolic activation studies (i.e. co-incubation with either S9, microsomes or hepatocytes), spleen cells were washed free of CCl4 immediately following the co-incubation period. Control splenocyte cultures (i.e. no metabolic activation system) incubated in the presence of CCl4 alone at 3.0 mM over a 3-h time-period, had no effect on spleen cell function, number or viability. In agreement with our previous findings which indicate that pretreatment of mice with inducers and inhibitors of the mixed function oxygenase system prior to CCl4 administration modulated the immunotoxic effects of CCl4 in vivo, these results lead us to conclude that immunotoxicity by CCl4 requires metabolic activation.
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PMID:The role of metabolism in carbon tetrachloride-mediated immunosuppression. In vitro studies. 146 54

The effects of all-trans-retinoic acid were investigated on the immune responses in C57Bl/6 mice after daily oral administration for one week. In selected experiments the immunosuppressive chemicals, cyclophosphamide and cyclosporin A were used in conjunction with retinoic acid. Retinoic acid stimulated the production of antibodies against sheep red blood cells and DNP-Ficoll; however, retinoic acid did not reverse the depression caused by immunosuppressive chemicals. In non-immunized animals retinoic acid stimulated the production of IL-1 but not of IL-2. The mitogenic responses of splenocytes against concanavalin A, phytohemagglutinin and pokeweed mitogen were depressed after the retinoic acid treatment; those against lipopolysaccharide were not influenced. Treatment with retinoic acid did not alter the mixed leukocyte responses but increased the activity of NK cells. Results indicate that retinoic acid may act as an adjuvant via activating macrophages, however, retinoic acid cannot reverse the immunosuppression induced by potent chemicals.
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PMID:Adjuvant activity of all-trans-retinoic acid in C57Bl/6 mice. 162 15

Mast cells and basophils have been known to play a central role in allergic inflammation through the release of chemical mediators by cross-linkage of IgE receptors. The IgE receptor triggering and calcium ionophore A23187 have also been shown to induce gene expression and production of tumor necrosis factor (TNF) by rat basophilic leukemia cells. In the present study, we examined whether IgE receptor triggering could induce gene expression and production of TNF in rat lung tissue. The lung tissue released not only histamine but also cytotoxic activity on L929 cells 2 and 4 h after incubation with dinitrophenyl conjugated to ovalbumin (DNP-OVA) following passive sensitization with anti-DNP monoclonal rat IgE antibody, whereas neither DNP-OVA nor anti-DNP IgE antibody could induce the cytotoxic activity when used solely. Calcium ionophore A23187 also could induce both histamine release and cytotoxic activity. These activities induced by IgE receptor triggering, A23187, and lipopolysaccharide were completely neutralized by preincubation with anti-mouse TNF-rabbit serum, but not with normal rabbit serum. Northern blot analysis using cDNA probe of mouse TNF demonstrated expression of TNF gene as early as 2 h after IgE receptor triggering. These data demonstrating that IgE receptor triggering induced gene expression and production of TNF in lung tissue suggest the participation of TNF in the pathogenesis of late asthmatic response through its biologic activities such as the attraction and activation of neutrophils and eosinophils.
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PMID:Production of tumor necrosis factor with IgE receptor triggering from sensitized lung tissue. 169 98

When highly purified human and murine B cells are challenged in vitro with certain so called "T cell-independent" activators such as the polyclonal B cell activator lipopolysaccharide (LPS) or the clonally specific B cell activator dinitrophenyl-conjugated polymerized flagellin (DNP-POL), mouse, but not human, cells differentiate into immunoglobulin-secreting cells. However, results from this study show that DNP-POL can cause human B cell differentiation in a T cell-independent manner when the antigen is concentrated onto the cells via artificially incorporated palmitate-modified anti-DNP mouse IgA molecules. This response is comparable in magnitude to that induced by a T cell-dependent polyclonal B cell activator, pokeweed mitogen, in unfractionated mononuclear cell cultures, suggesting that DNP-POL induced polyclonal B cell differentiation. DNP-POL binding to the artificial receptor molecules on B cells did not cause cellular proliferation, even in unfractionated mononuclear cell populations. These results are similar to those obtained in previous studies using mouse B cells in which the artificial receptor was unable to act as a transmembrane signaling element. From these studies, we conclude that B cells express clonally unrestricted, presumably low-avidity, endogenous receptor for POL, and that signaling through this receptor activates B cell differentiation but not cell proliferation.
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PMID:Antigen activation of human B lymphocytes bearing artificial antigen receptors. 176 7

Monocrotaline (MCT) is a member of a class of naturally occurring phytotoxins known as pyrrolizidine alkaloids, and is a toxicological concern to both man and his livestock. The purpose of these studies was to evaluate the effect of a 14-day oral MCT (0-100 mg/kg per day) exposure on the functional integrity of various immunocyte effector systems in C57BL/6 mice, as well as to investigate potential mechanisms for its immunotoxicity. Decreases in lymphoid organ weights and cellularity, and resident peritoneal exudate cell (PEC) number were only observed after exposure to the highest dose of 100 mg/kg MCT. This dose also inhibited NK cell cytotoxicity, while the total number of NK lytic units per spleen was decreased (-53%) after exposure to 50 mg/kg MCT. Following i.p. injection of SRBC, the percentage of PEC macrophages containing engulfed SRBC was significantly increased in MCT-exposed mice, while the percentage of large vacuolated (activated) macrophages was decreased in a dose-dependent manner. Exposure to MCT significantly decreased the total number of Ig+ cells without altering the number of CD4+ and CD8+ cells. The antibody responses (PFC/10(6) spleen cells) to two T cell-independent antigens, TNP-LPS and DNP-Ficoll, were significantly decreased at all MCT doses, and the degree of suppression of both responses was identical at coincident doses. MCT exposure (25 mg/kg) significantly suppressed the blastogenic response to the T cell mitogen concanavalin A (-38%), and to the B cell mitogen lipopolysaccharide (-58%). These results indicate that exposure to MCT can alter the functional integrity of various immune effector responses in a dose-dependent manner, and suggest that the B cell may be a relatively more sensitive target of MCT immunotoxicity compared to T cells, macrophages and NK cells.
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PMID:Tier-2 studies on monocrotaline immunotoxicity in C57BL/6 mice. 177 39

2',3'-Dideoxyadenosine (ddA) is a nucleoside analogue with anti-HIV activity and one of its metabolic products, 2',3'-dideoxyinosine (ddI), has shown promising results in clinical trials for the treatment of acquired immunodeficiency syndrome (AIDS). Because AIDS viruses target the immune system, it is important to understand the potential effects of anti-AIDS drugs, including natural nucleosides, on the immune system. Previous immunotoxicological studies have shown that 22 treatments with ddA to female B6C3F1 mice over a period of 30 days had no effect on cell-mediated immunity, including the mixed lymphocyte reaction and response to mitogenic signals, but suppressed in vitro IgM plaque-forming cell (PFC) response to sheep red blood cells. The present studies show that suppression of the IgM PFC response was dose dependent with a 96% reduction in IgM PFCs/10(6) spleen cells at the highest dose (350 mg/kg). The in vivo IgM PFC response to DNP-Ficoll and the in vitro IgM PFC response to lipopolysaccharide, both T-independent antigens, were also suppressed in the spleens of ddA-treated mice. The analysis of splenocyte subtypes shows no change in the percentage of B cells (surface immunoglobulin positive cells), T helper cells (L3T4 positive cells), and T suppressor cells or T cytotoxic cells (Lyt-2 positive cells) in the spleens of ddA-treated mice. In vitro separation and reconstitution studies in which the IgM PFC response was monitored indicated that the B lymphocyte rather than the T lymphocyte or antigen-presenting cell is the primary cell targeted by ddA. This information provides a data base for further mechanistic study and may reflect on the clinical use of other nucleoside analogues, e.g., ddI by providing the clinician with information indicating the potential decrease in humoral immunity.
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PMID:The B lymphocyte is the immune cell target for 2',3'-dideoxyadenosine. 223 21


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