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 formation of anti-DNA antibodies appears to be under a genetic control similar to that regulating the immune response to complex antigenic compounds. The ability to develop a high immune response to DNA seems to be predominantly dependent on the nature of the B-cell population whereas a major role of the T-cell suppressor population is not evident in this response. The immune response to DNA does not necessarily need the presence of thymus-derived lymphocytes, but in some cases T-cells may exert a helper effect. The development of anti-DNA antibody response may be triggered by various factors: viral, bacterial or parasitic agents, tissue destruction or some drugs. A mechanism that may play an important role is the "nonspecific" triggering of anti-DNA antibodies by substances that, like bacterial lipopolysaccharides, exert a potent stimulatory effect on B-cells and simultaneously induce a release of DNA in extracellular fluids. In lupus diseases as well as in mice injected with lipopolysaccharide, pathogenic effects of anti-DNA antibodies appear to be closely related to the formation of DNA-anti-DNA complexes. The demonstration that injections of lipopolysaccharide lead to the localization of DNA-anti-DNA complexes in kidney glomeruli stressed the possible importance of stimuli responsible for a release of DNA in circulating blood in the expression of the pathogenic effects of anti-DNA antibodies.
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PMID:Genesis and pathogenicity of anti-DNA antibodies. 13 82

It is widely believed that autoimmunity is an integral part of the immune system, and that genetic, immunologic, hormonal, environmental and other factors contribute to the pathogenesis of autoimmune disease. Thus, autoimmune disease may represent an abnormal expression of immune functions instead of loss of tolerance to self, and it can be organ specific or systemic in its manifestations. We review the various factors that contribute to the development of autoimmune disease; we also review the mechanisms of polyclonal B-cell activation, with emphasis on the role of infectious agents. We consider systemic lupus erythematosus in humans and in experimental animals as prototypic autoimmune disease, and we summarize data to indicate that polyclonal B-cell activation is central to the pathogenesis of systemic autoimmune disease. The effect of polyclonal B-cell activation, brought about by injections of a B-cell activator-lipopolysaccharide from Gram-negative bacteria-is sufficient to cause autoimmune disease in an immunologically normal host. In fact, autoimmune disease can be arrested if excessive polyclonal B-cell activation is suppressed; alternatively, autoimmune disease can be exacerbated if polyclonal B-cell activation is enhanced. We explore the mechanism of tissue injury when autoimmune disease is induced or exacerbated, and we consider the pathogenic roles of autoantibodies, immune complexes, complement, the blood cell carrier system, and the mononuclear phagocyte system. Although polyclonal B-cell activation may be the mechanism whereby various factors can cause or exacerbate systemic autoimmune disease, polyclonal B-cell activation may cause autoimmune disease on its own.
Lupus 1992 Feb
PMID:Autoimmunity, polyclonal B-cell activation and infection. 130 66

We investigated the role of immunoglobulin isotypes in the exacerbation of lupus nephritis associated with exposure to bacterial lipopolysaccharide. The data indicate that enhanced polyclonal B-cell activation and exacerbated autoimmune disease evoked by lipopolysaccharide are associated with an increase in the concentration of isotypes in plasma and in renal eluate, that this isotype response is polyclonal and preferential but not restrictive, that all B cells are responsive but all are not equally sensitive to the effects of lipopolysaccharide, and that some expanded isotypes may be more nephritogenic in certain strains of lupus-prone mice.
Lupus 1992 Aug
PMID:Bacterial lipopolysaccharide causes variable deposits of diverse immunoglobulin isotypes in kidneys of lupus-prone mice. 130 89

Human TNF alpha locus locates between HLA-B and DR region on the short arm of chromosome 6. The 5.5 kb and 10.5 kb of TNF alpha restriction fragment length polymorphic (RFLP) bands were identified by Southern hybridization using a restriction enzyme, NcoI. The frequencies of those bands were not different among patients with systemic lupus erythematosus (SLE), those with rheumatoid arthritis and normal controls. In the lupus patients, proteinuria was more frequent in the patients with the 5.5 kb RFLP band (19/39: 48.7%) than those without 5.5 kb band (7/35: 20%) (p less than 0.05). Furthermore, this band was strongly associated with the haplotype HLA B44-DRw13-DQw1. In order to investigate the association between this gene polymorphism and the production of TNF alpha, peripheral blood mononuclear cells from patients with SLE and normal controls were cultured for 24 hours with lipopolysaccharide and concanavalin A and the amount of TNF alpha in the supernatant was measured by enzyme linked immunosorbent assay. The TNF alpha production of lupus patients was not statistically different from that of normal controls. The production of TNF alpha was not related to 5.5 kb RFLP band, but in the patients with SLE, the mean value of TNF alpha in patients with the 5.5 kb RFLP band tended to be higher than those without the band. Lupus patients were divided into two groups by the production of TNF alpha i.e. low TNF alpha inducibility group and high TNF alpha inducibility group. Patients with proteinuria were more frequent in patients of the high TNF alpha inducibility group than those of low TNF alpha inducibility group (p less than 0.05). There were four patients with HLA B44-DRw13-DQw1 who had the 5.5 kb RFLP band and three of them belonged to the high TNF alpha inducibility group with nephrosis. These data suggest that TNF alpha and HLA are possibly associated with the severity of lupus nephritis.
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PMID:[Tumor necrosis factor alpha in systemic lupus erythematosus: evaluation by restriction fragment length polymorphism and production by peripheral blood mononuclear cells]. 135 65

Systemic autoimmune disease is influenced by genetic, immunological, hormonal, and environmental factors. Although environmental factors are major agents that induce or exacerbate autoimmune diseases, the mechanism(s) and the molecular events by which they operate remain poorly understood. Here we used the lupus-prone BXSB mouse as an animal model of systemic autoimmune disease, and we used a bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism(s) by which infectious agents exacerbate autoimmune diseases. Our experimental protocol was designed to address three questions: (i) whether spontaneous polyclonal B cell activation (PBA) that occurs in BXSB mice could be further enhanced by bacterial LPS; (ii) whether repeated exposure to LPS would exacerbate autoimmune disease, as reflected by enhanced deposits of immune complexes (ICs) in kidneys and exacerbated nephritis; and (iii) whether the mechanism by which LPS exacerbates nephritis might involve interference with blood cell carrier function, mononuclear phagocyte function, or both. BXSB mice were injected with LPS (25 micrograms) twice a week for 5 weeks; control autoimmune BXSB mice and immunologically normal (C57BL/6) mice were injected with vehicle only. The three groups of mice were then challenged with soluble ICs to assess the kinetics of their disappearance from the circulation, their uptake by the mononuclear phagocyte system (liver, spleen), their distribution in target organ (kidney), and blood cell carrier function. The results indicate that: (i) spontaneous PBA can be enhanced further by LPS; (ii) exposure to LPS results in increased deposits of endogenous ICs in kidneys and exacerbated nephritis; and (iii) defective handling of ICs by the mononuclear phagocyte system and impaired blood cell carrier function are contributory factors to exacerbated nephritis, but that mechanisms in addition to passive localization of ICs may also be operative.
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PMID:Bacterial lipopolysaccharide enhances deposition of immune complexes and exacerbates nephritis in BXSB lupus-prone mice. 186 8

The precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB x NZWF1 (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti-DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus.
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PMID:Qualitative difference of anti-DNA antibody-producing cell precursors in the pre-immune B cell repertoire between normal and lupus-prone mice. 191 23

Polyclonal B cell activation (PBA) and autoimmune disease can be induced in immunologically normal mice, or enhanced in lupus-prone mice, by bacterial lipopolysaccharide (LPS). Because immune defects are common in autoimmune diseases and IgA deficiency is prevalent in patients with systemic lupus erythematosus, we investigated: (i) whether LPS might induce IgA deficiency in normal mice; (ii) whether IgA deficiency might be a feature in lupus-prone mice; (iii) whether, if present in lupus-prone mice, IgA deficiency could be further accentuated by LPS; and (iv) whether the effects of LPS on IgA concentrations of normal and lupus-prone mice might be reversible upon withdrawal of LPS. We injected normal (C57BL/6) and lupus-prone (NZB/W) mice with 50 micrograms of LPS from Salmonella minnesota Re595 twice a week for 5 weeks and then discontinued LPS for 6 weeks. We determined the concentrations of plasma immunoglobulins, DNA antibodies, and circulating immune complexes before, during, and after mice were exposed to LPS. Our results indicate that: (i) LPS induces IgA deficiency in normal mice concurrently with PBA; (ii) IgA deficiency is a feature of lupus-prone mice; (iii) LPS accentuates naturally occurring PBA and IgA deficiency in lupus-prone mice; and (iv) LPS induced, or LPS enhanced, IgA deficiency and PBA in normal and lupus-prone mice persist long after withdrawal of LPS. Thus, LPS triggers or enhances autoimmune disease by a mechanism that involves in part PBA with selective increase (IgG, IgM) and concurrent decrease (IgA) of specific isotypes.
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PMID:Bacterial lipopolysaccharide induces long-lasting IgA deficiency concurrently with features of polyclonal B cell activation in normal and in lupus-prone mice. 201 4

Cyclophosphazenic compounds bearing ethylene-imino groups are cytocydal chemicals which can modulate polyclonal activation of lymphocytes (PAL) and prevent the development of murine lupus. The effects on PAL of the different parts of these chemicals and of vectorization by polyamines have been investigated by treating lipopolysaccharide injected C57Bl/6 mice with various cyclophosphazenic compounds and thiotepa. The immune effects of the cyclophosphazenic substances have been found to be mediated by ethylene-imino groups and to be modulated by polyamine vectorization. These compounds might represent a new class of drugs for treatment of immune mediated diseases of the lupus type.
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PMID:Modulation of polyclonal activation of lymphocytes by cyclophosphazenic compounds bearing ethylene-imino groups and vectorized by polyamines. 221 Sep 15

Depletion of B cells in mice bearing the lymphoproliferation (lpr) gene reduces lymphoproliferation and polyclonal B cell activation (PBA) and attenuates mononuclear cell vasculitis. We sought to verify whether the obverse was true, i.e. whether enhancement of B cell activity might exacerbate the nephritis of MRL/lpr (MRL) mice, a lupus-prone strain. The experimental approach was designed to address three questions: whether naturally occurring PBA in MRL mice could be further enhanced; whether enhanced PBA would exacerbate nephritis; and whether the mechanism of nephritis exacerbation involved interference with mononuclear phagocyte system (MPS) function. To enhance B cell activity, we injected MRL mice with lipopolysaccharide (LPS) from Gram-negative bacteria, a potent B cell activator. To determine whether nephritis was exacerbated, we performed immunopathologic studies and tests of renal function. To verify whether nephritis exacerbation involved impairment of MPS function, we probed the kinetics of immune complex removal from the circulation, their uptake by the liver and spleen, and their localization in kidney tissue. The results indicate that in MRL mice: (i) spontaneous PBA can be enhanced by LPS; (ii) enhancement of PBA by LPS exacerbates nephritis; and (iii) the MPS is already saturated, presumably due to excessive production of endogenous immune complexes. Thus, further increase in immune complex formation due to enhanced PBA by LPS results in increased localization of immune complexes in kidneys and exacerbated nephritis.
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PMID:Lipopolysaccharide from gram-negative bacteria enhances polyclonal B cell activation and exacerbates nephritis in MRL/lpr mice. 226 89

In the present study, we found the expression of transcripts homologous to Abelson murine leukemia virus (A-MuLV) in lupus-prone mice and nonautoimmune mice. One of them, as the lupus-related transcript, is expressed in only lupus-prone mice and induced by bacterial lipopolysaccharide (LSP). We could not induce the transcript by LSP in nonautoimmune mice that we examined. The significance of the transcript autoimmune events in lupus-prone mice is discussed.
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PMID:Lupus-related transcript homologous to Abelson-murine leukemia virus. 245 5


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