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)

T cells from murine lupus strains manifest complex defects in interleukin 2 (IL 2) production and receptor expression. The capacity of B cells from such mice to utilize IL 2 as a growth factor has not been previously reported and is examined herein. Anti-Thy-1.2 plus complement-treated spleen cells from 6-8-week-old autoimmune MRL-lpr/lpr mice and from age and sex-matched immunologically normal CBA/J mice were cultured with lipopolysaccharide (LPS) for 36 h and analyzed for the expression of IL 2 receptors using the monoclonal antibody 7D4. The percentage of B cells expressing IL 2 receptors was comparable in MRL-lpr/lpr and CBA/J mice. In contrast to those from CBA/J, BALB/c and (BALB/c X NZW)F1 mice, LPS-stimulated B cells from MRL-lpr/lpr and from (NZB X NZW)F1 mice were capable of proliferating in response to IL 2. Fractionation of MRL-lpr/lpr B cells using Percoll gradient density separation demonstrated that the IL 2-responsive population consisted predominantly of large cells. In addition, unfractionated B cells from MRL-lpr/lpr mice were found to be substantially more responsive to IL 2 than those from CBA/J and BALB/c mice following activation with anti-immunoglobulin plus LPS. The hyper-responsiveness to IL 2 may be a consequence of the state of activation of autoimmune B cells and is of potential importance in the pathogenesis of systemic lupus erythematosus.
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PMID:Interleukin 2 is a proliferative signal for B cells from autoimmune mice. 309 46

Activation/proliferation of mouse and human T and B cells is associated with expression and subsequent release of interleukin 2 receptors (IL 2R) into the milieu. The soluble form of IL 2R, at least in part, retains its ability to bind to IL 2 and to anti-receptor antibodies, but its exact structure remains unknown. Because systemic lupus erythematosus (SLE) is associated with T and B cell activation, we have used monoclonal anti-IL 2R antibodies in an ELISA to measure levels of IL 2R in sera of various lupus strains. High levels of the released receptor were found at an active clinical stage in sera of four autoimmune strains of mice homozygous for the lpr (lymphoproliferation) gene that causes T cell expansion, massive lymphoid organ enlargement, and promotes the autoimmune process. High levels were also found in lupus mice characterized primarily by B cell proliferation (BXSB males) and in (NZB X W)F1 mice characterized by T and B cell activation. Similarly high IL 2R serum levels could be induced experimentally in normal mice injected with immunostimulants such as bacterial lipopolysaccharide or Freund's complete adjuvant. The results indicate that IL 2R serum levels may provide a good marker of ongoing lymphoid cell activation/proliferation, and thus might be useful in the follow-up of patients with systemic autoimmune or other lymphoproliferative disorders. The biologic roles, if any, of the soluble form of IL 2R and its effects in normal and abnormal conditions remain to be determined.
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PMID:Elevated titers of cell-free interleukin 2 receptor in serum of lupus mice. 311 68

An assessment of the prophylactic and ameliorative effects of deoxyspergualin (NKT-01), an immunosuppressive agent, was carried out in male MRL/MpJ-lpr/lpr (MRL/1) mice which spontaneously develop lupus-like lesions. When NKT-01 was administered ip daily from the age of either 8 or 19 weeks, diseases such as massive lymphadenopathy, circulating anti-DNA antibody and lupus nephritis were markedly suppressed. The primary response to lipopolysaccharide was significantly reduced in MRL/1 mice administered NKT-01 but the response to sheep red blood cells was not affected. The ability of spleen cells to release interleukins 2 and 3 with or without mitogen was significantly enhanced in mice receiving NKT-01. These findings demonstrate that NKT-01 has therapeutic activity against the development of spontaneous disease in MRL/1 mice.
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PMID:Biological activities of deoxyspergualin in autoimmune disease mice. 326 48

Although ultraviolet (UV) light is generally harmful to patients with systemic lupus erythematosus, most clinical and immunologic studies of UV exposure have evaluated the effects of UV-B (280-320 nm). The long-wavelength UV-A band (320-400 nm), however, is less toxic than UV-B and has different immunologic actions. Therefore, we studied the effect of UV-A irradiation on survival and immunologic function in the (New Zealand black x New Zealand white)F1 hybrid mouse model of systemic lupus erythematosus. Twenty-one (New Zealand black x New Zealand white)F1 mice were treated with 3.5 joules/cm2/day of UV-A light for 5 days each week, beginning at age 10 weeks. A control group consisted of 20 untreated animals. All UV-A-irradiated mice survived to 32 weeks, compared with 12 of 20 mice in the nonirradiated group (P = 0.0013). Splenomegaly was significantly decreased in the irradiated mice (P less than 0.03). Mice that received UV-A treatment combined with depilation had significantly improved lymphocyte responses to phytohemagglutinin and lipopolysaccharide and significantly decreased levels of anti-DNA antibodies compared with mice that received neither treatment. Reductions in spleen size and anti-DNA antibody titer were significantly correlated with improved parameters of lymphocyte function. These results suggest that a relatively small dose of UV-A exerts significant therapeutic action in murine lupus, perhaps through an effect on immunologic regulation.
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PMID:Ultraviolet-A light prolongs survival and improves immune function in (New Zealand black x New Zealand white)F1 hybrid mice. 359 37

Anti-histone antibodies (AHA) are spontaneously produced in NZB/NZW mice as part of their autoimmune disease. IgM AHA are usually not detected until after 4 mo of age, and older female mice switch to the production of IgG AHA. We studied the in vitro production of AHA by spleen cells from young (less than or equal to 12-wk-old) NZB/NZW mice. Despite the absence of elevated serum AHA activity, spleen cells from these mice demonstrated marked spontaneous autoantibody production in culture. In kinetic studies, little in vitro production was detectable after 1 day of culture, and maximal accumulation occurred on day 5. Elevated AHA production was apparent by cells from 2-wk-old NZB/NZW mice, and an age-dependent increase in autoantibody production was also noted. Only AHA of the IgM class were detected in cultures of young spleen cells. The in vitro production of IgM AHA in culture was T cell dependent, depletion of T cells resulting in a 70 to 90% reduction in production, which was corrected by the readdition of T cells. In cultures where both IgM AHA and total IgM secretion were measured, a much greater T cell dependence for AHA production was apparent. The requirement for T cells could also be partially replaced by factors present in concanavalin A supernatant. AHA secretion was induced by lipopolysaccharide by using cells from both NZB/NZW and non-autoimmune mice. Although production was greater with NZB/NZW cells, the difference was much less than that for spontaneous production. Thus, AHA-secreting cells that are dependent on in vitro T cell help are present in young NZB/NZW mice. These studies may help define the mechanisms responsible for selective autoantibody secretion in lupus-like disease.
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PMID:In vitro production of anti-histone antibodies by spleen cells from young autoantibody negative NZB/NZW mice. 387 28

A lupus-like disease characterized by a severe immune complex glomerulonephritis and IgG autoantibody production was induced in (C57BL/6 X DBA/2)F1 mice by injection of parental DBA/2 lymphoid cells. The ensuing graft-vs-host (GVH) reaction resulted in a 10- and a 100-fold increase in serum IgG antibody levels to denatured DNA and total histones, respectively, compared with that in F1----F1 control mice. The level of anti-DNA antibodies peaked 2 wk after injection of DBA/2 cells and preceded peak anti-histone levels by approximately 2 wk. Anti-histone antibodies were generated predominantly to histones H1, H2A, and H2B, a profile different from that observed in NZB/NZW and MRL-lpr/lpr mice. The marked increase in IgG antinuclear antibodies did not correlate with increases in total IgG serum levels and was not associated with comparable increases in antibodies to transferrin, hemoglobin, fibrinogen, or thyroglobulin. Selective autoantibody production was also observed in vitro, wherein GVH spleen cells produced high levels of IgG antibodies to total histones and denatured DNA but not to these non-nuclear protein antigens. In contrast, spleen cells stimulated in vitro with lipopolysaccharide produced equivalent amounts of antibodies to all antigens tested. Our results are in agreement with those of other investigators and collectively suggest that IgG autoantibodies in GVH disease, and possibly in spontaneous lupus-like disease, are not secondary to a generalized B cell activation, but may be selectively generated in response to self antigens with unique configurational properties.
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PMID:Autoimmunization in murine graft-vs-host disease. I. Selective production of antibodies to histones and DNA. 387 58

Sera from patients with systemic lupus erythematosus and from mice spontaneously developing lupus were subjected to isoelectric focusing by a microsucrose gradient method. The spectrotypes of human antibodies to native DNA, denatured DNA, and polyriboadenylic acid (poly A) were compared. Antibodies to native DNA and denatured DNA focused into two regions whose boundaries were pH 5.0-7.0 and pH 8.5-10.0. Antinative DNA antibodies were more homogeneous than antidenatured DNA antibodies. Anti-DNA antibodies in cryoglobulins showed more restriction than those present in serum. There was no relationship between spectrotype and pattern of disease expression. Murine antibodies to native DNA were more heterogeneous than human anti-DNA antibodies. The spectrotypes of antidenatured DNA antibodies from patients with systemic lupus erythematosus or drug induced lupus, or from an immunized rabbit, were similar. Likewise, antibodies to poly A were similar in both human and murine lupus. In contrast to anti-DNA, antibodies to poly A were restricted and focused only in the alkaline range (pH 9.5-10.0). The spectrotype of antipoly A antibodies induced by lipopolysaccharide were comparable but had an additional small band at pH 6.2. Our results suggest unique antibody spectrotypes with varying degrees of restriction for different nucleic acid antigens. Furthermore, spontaneous and induced autoantibodies have similar spectrotypes. Thus, the B cell clones producing antinucleic acid antibodies may be similar whether they are activated spontaneously, following immunization, or as a consequence of polyclonal stimulation.
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PMID:Comparison of different antinucleic acid antibody spectrotypes in spontaneous, induced, and murine lupus. 616 39

B cell hyperactivity, a feature common to all lupus-prone murine strains, may be caused by hyperresponsiveness to, overproduction of, or bypassing of certain signals required for B cell activation, proliferation, and differentiation. In this study, we have compared the responses of B cells from three lupus-prone strains of mice (BXSB males, MRL and NZB/W females) and normal strains in a number of assays for which two or more signals are required to obtain a response. In medium to low density cultures of B cells from BXSB and NZB/W but not MRL/l lupus mice, the cells' proliferation induced by bacterial lipopolysaccharide (LPS) or anti-mu antibody was much higher than that of B cells from normal controls. At low B cell density, polyclonal activation by these substances and subsequent Ig secretion were dependent on accessory signals present in supernatants of concanavalin A-treated normal lymphocytes (CAS) or on the MRL/l proliferating T cell-derived B cell differentiation factor (L-BCDF) in both lupus-prone and immunologically normal mice. However, the responses of B cells from BXSB and NZB/W, but not MRL/l, mice to these accessory signals were higher than those of normal mice. Ig synthesis by fresh B cells of BXSB and NZB/W mice cultured in the absence of mitogens but in the presence of CAS or L-BCDF was higher than by similar cells from other strains, suggesting an increased frequency of B cells activated in vivo in these two autoimmune strains of mice. The patterns of IgG subclass secretion in response to LPS (without added CAS or L-BCDF) were abnormal in all lupus strains, with a predominance of IgG2b and/or IgG2a and low levels of IgG3, contrary to normal B cells for which IgG3 synthesis predominated. However, IgG1 synthesis in vitro by autoimmune and normal B cells alike was highly dependent on T cell-derived soluble mediators. Antigen-specific responses to SRBC in vitro of B cells from all lupus strains, like those of B cells from normal strains, required a minimum of three signals (antigen, LPS, T cell-derived antigen nonspecific helper factors). Yet, once triggered, B cells of BXSB and NZB/W mice gave higher responses than those of the other strains. We conclude that B cells of lupus mice have signal requirements similar to those of normal mice. Nevertheless, B cells of BXSB and NZB/W, but not MRL/l, lupus mice hyperrespond or process some accessory signals abnormally.
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PMID:B cell dependence on and response to accessory signals in murine lupus strains. 640 39

Palmerston North (PN) mice, a newly recognized model of systemic lupus erythematosus, were compared with autoimmune hybrid NZB/NZW mice in a study designed to examine spleen cell responsiveness to T-cell and B-cell mitogens. Modest reductions of responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were noted in PN females after 24 weeks of age; these responses were reduced significantly in NZB/NZW females. In contrast, male PN and NZB/NZW mice responded actively to PHA and Con A throughout the first year of life. Responses to lipopolysaccharide were not affected by age or sex. Anti-DNA antibody levels, blood urea nitrogen, and glomerular histology were analyzed to determine if autoantibody production or renal failure correlated with suppressed mitogenic responsiveness. These factors, examined singly and together, were not as important as age. In this system, age and sex did not influence spleen cell responses to mitogens in normal CD-1 mice. Age and sex were of minimal importance in determining responses to T-cell mitogens in the recently defined PN model of autoimmunity. In contrast, age and sex exerted strong influences upon responses to PHA and Con A in the NZB/NZW model of lupus.
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PMID:Responses to T-cell and B-cell mitogens in autoimmune Palmerston North and NZB/NZW mice. 660 3

Weekly injections of cyclophosphamide (Cy) at a dose of 20 mg/kg body weight prevented IgM to IgG class switch of serum anti-DNA antibodies and also immunoglobulin secreting cells in the spleen of MRL/Mp-lpr/lpr (MRL/1) mice. Culture experiments revealed that splenic B cells of Cy treated mice gave rise to more IgM and less IgG secreting cells than those of untreated mice in response to lipopolysaccharide. These results suggested that Cy suppressed enhanced differentiation of B cells into IgG secreting cells in MRL/1 mice, which would result in reduction of IgG anti-single stranded DNA antibodies and improvement of murine lupus like syndrome.
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PMID:Long term administration of cyclophosphamide into MRL/1 mice. II. The effects on the isotype of anti-DNA antibodies and immunoglobulin secreting cells in the spleen. 660 25


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