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)

Proliferative responses of naive splenocytes to Borrelia burgdorferi antigens from mice susceptible (C3H) and resistant (BALB) to Lyme borreliosis were investigated. B. burgdorferi spirochetes and recombinant outer surface proteins, OspA and OspB, were found to induce nonspecific proliferation of naive splenocytes from both strains of mice. Cell purification studies localized nonspecific proliferation to the B cell-enriched fraction. B. burgdorferi, OspA, and OspB were found to induce IgM and IgG synthesis in vitro. The mitogenic effect of B. burgdorferi was dissimilar to that of lipopolysaccharide (LPS), in that B cells from C3H/HeJ mice (LPS-unresponsive) responded at levels comparable to those from C3H/HeNCrlBr mice. These results emphasize the need for caution in the study of antigen-specific proliferation for B. burgdorferi.
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PMID:Nonspecific proliferative responses of murine lymphocytes to Borrelia burgdorferi antigens. 152 33

SDS-PAGE and Western immunoblot profiles have been determined for different strains of Borrelia burgdorferi. Major proteins of 60 kDa, 41 kDa corresponding to flagellin, 34-36 kDa and 30-31 kDa corresponding to OspB and OspA respectively, and 18-20 kDa corresponding to 'pC' fractions were detected. A "rough" lipopolysaccharide which we called lipooligosaccharide (LOS) of 8-11 kDa appeared to be present, being detected by specific silver staining, as in crude Borrelia lysates as in proteinase K digested Borrelia strains, quite similar in shape among the different strains examined. The LOS reacted in Western blotting with immune anti-B. burgdorferi rabbit serum and also with sera collected from humans affected by Lyme borreliosis. The LOS did not react with sera positive for syphilis or leptospirosis, and their immunological specificity is discussed.
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PMID:Evidence for (lipo) oligosaccharides in Borrelia burgdorferi and their serological specificity. 171 76

Lyme disease refers to the multisymptomatic illness in humans which results from infection with the tick-borne spirochete Borrelia burgdorferi. The white-footed mouse is the major reservoir for B. burgdorferi and, upon infection, certain inbred mice develop symptoms similar to those reported in human disease. Sonicated preparations of washed spirochetes were found to have potent mitogenic activity when cultured with lymphocytes from naive C57BL/6, C3H/HeJ, or BALB/c mice. The activity of the B. burgdorferi sonicate was approximately fourfold greater than that of a similarly prepared Escherichia coli sonicate. Polymyxin B efficiently inhibited the mitogenic activity of the E. coli sonicate but only slightly inhibited that of the B. burgdorferi sonicate, suggesting that a lipid A-containing lipopolysaccharide was not responsible for the B. burgdorferi activity. Kinetic analysis indicated peak proliferation at 2 to 3 days of culturing, suggesting polyclonal activation. B- and T-lymphocyte depletion experiments indicated that the major cell type responding to the B. burgdorferi mitogen was the B lymphocyte. This mitogen stimulated murine B cells not only to proliferate but also to differentiate into antibody-secreting cells, as demonstrated by the production of immunoglobulin by stimulated splenocytes. Furthermore, the sonicated preparation stimulated the B-cell tumor line CH12.LX to secrete immunoglobulin in the absence of accessory cells. B. burgdorferi also stimulated interleukin-6 production in splenocyte cultures. The observation that B. burgdorferi can stimulate activation of and immunoglobulin production by normal B lymphocytes may directly reflect on the development of arthritis associated with persistent infection by this organism.
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PMID:Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, Borrelia burgdorferi. 173 Apr 76

To investigate the role of interleukin 1 (IL-1) in Lyme arthritis we assayed synovial fluids (SF) for the presence of IL-1 activity. Crude SF from patients with Lyme disease showed IL-1-like activity. Chromatography of joint fluids revealed activity at 15-20,000 daltons. Two populations of cells were grown, which produced significant IL-1 activity when stimulated with the Lyme disease spirochete or its lipopolysaccharide. IL-1 activity from SF or stimulated cells was neutralized with an antihuman IL-1 antibody. Our results suggest IL-1 is important in the pathogenesis of Lyme arthritis, and is similar to other arthritides.
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PMID:Isolation of interleukin 1 from joint fluids of patients with Lyme disease. 278 87

Interleukin-1 (IL-1) is the major immunoregulatory molecule produced by macrophages in response to a variety of environmental insults including chemicals, phagocytosis, bacteria, and bacterial products. Macrophages stimulated by Borrelia burgdorferi produced large quantities of IL-1 when spirochetes were added to macrophages at a ratio of 10 spirochetes per macrophage. The release of IL-1 was dose dependent: a single spirochete per macrophage was sufficient to produce significant quantities of IL-1. Spirochetal lipopolysaccharide was not required for this activity in that polymyxin B in the spirochete-macrophage culture had no effect on IL-1 production. Normal murine fibroblasts cultured with this IL-1 were shown to have an increased rate of DNA synthesis and an increase in secreted collagenase. IL-1 was found in joint fluids from Lyme disease patients. When IL-1 was injected intradermally into the backs of rabbits, the injection sites became indurated, erythematous, and warm to the touch after 4 hrs and annular lesions much like those of erythema chronicum migrans were seen in some animals after 24 hrs. B. burgdorferi is a powerful inducer for IL-1 in vitro, and it is reasonable to presume that it acts similarly in Lyme disease patients. Our results suggest that IL-1 in turn, may play a role in many of the clinical manifestations of Lyme disease.
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PMID:A role for interleukin-1 in the pathogenesis of Lyme disease. 349 83

We were unable to demonstrate the presence of the classic enterobacterium-type lipopolysaccharide in the cells of the Lyme disease spirochete, Borrelia burgdorferi B31. This finding was primarily based on chemical analysis and the absence of free lipid A upon mild acid hydrolysis of the appropriate cell extracts. These results do not preclude the possible existence of an unusual lipopolysaccharide-like compound(s) in B. burgdorferi.
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PMID:Absence of lipopolysaccharide in the Lyme disease spirochete, Borrelia burgdorferi. 362 5

A lipopolysaccharide (LPS) was isolated from the Lyme disease spirochete by a modification of the hot phenol-water method. The material was composed of 45% carbohydrate, 8% protein, 44% lipid A, and 1% 3-deoxy-D-mannooctulosonic acid and accounted for approximately 1.5% of the cellular dry weight. The isolated LPS possessed several biologic activities characteristic of endotoxins. The LPS was pyrogenic for rabbits, mitogenic for human mononuclear cells and murine splenocytes, capable of clotting limulus lysate, and cytotoxic for murine macrophages. LPS extracted from Borrelia burgdorferi by the petroleum-ether:chloroform:liquid-phenol procedure was also characterized. The results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro, and the expression of such activities in vivo may play an important role in the pathogenesis of Lyme disease. Some of the clinical manifestations of other spirochetal disease may be explained by similar endotoxins in those organisms. To our knowledge this is the first report of an LPS extracted from a spirochete that is known to be a human pathogen.
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PMID:Chemical and biologic characterization of a lipopolysaccharide extracted from the Lyme disease spirochete (Borrelia burgdorferi). 400 83

The membrane lipoproteins of Treponema pallidum and Borrelia burgdorferi have potent immunostimulatory properties in vitro, implicating them as major inflammatory mediators in syphilis and Lyme disease. Recently, we reported that synthetic lipohexapeptide analogs (lipopeptides) of the lipoproteins could be used as surrogates for native spirochetal lipoproteins in immune cell activation studies in vitro. The present study was designed to evaluate the inflammatory properties of the lipopeptides in vivo and to correlate the cellular responses to these synthetic analogs with the histopathology of syphilis and Lyme disease. Lipopeptides corresponding to the 47-kDa major membrane lipoprotein of T. pallidum and the outer surface protein A of B. burgdorferi injected intradermally induced dose-dependent dermal inflammation in mice; the initial predominantly neutrophilic (mice) or heterophilic (rabbits) cellular infiltrates were followed by infiltrates consisting predominantly of mononuclear cells. The intradermal response of rabbits to the 47-kDa lipopeptide was strikingly similar to that observed for animals infected intradermally with T. pallidum. In all cases, lipopolysaccharide was substantially more potent as an inflammatory mediator than the spirochetal lipopeptides. In contrast to the lipopeptides, nonacylated hexapeptides elicited minimal or no dermal lesions in mice or rabbits, underscoring the importance of acyl modification to the inflammatory properties of the lipopeptides. This study provides the first in vivo evidence that the spirochetal lipoproteins/lipopeptides contribute to the immunopathogenesis of syphilis and Lyme disease.
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PMID:Dermal inflammation elicited by synthetic analogs of Treponema pallidum and Borrelia burgdorferi lipoproteins. 789 Apr 17

The proliferative response of peripheral blood T cells to the spirochete, Borrelia burgdorferi, can be as pronounced in unexposed normal individuals as it is in Lyme disease patients. This finding was observed using three geographically distinct isolates of B. burgdorferi. The response is not due to a lipopolysaccharide effect of the spirochete, is sensitive to Proteinase K, and requires antigen processing. It does not result from cross-reactivity of memory T cells that may be reactive to another antigen; the proliferative response to B. burgdorferi is equally distributed between naive (CD29-, CD45RO-) and memory (CD29+, CD45RO+) T cells, whereas the tetanus response is confined to the memory subset. In support of this notion, cord blood specimens that contain almost entirely naive T cells, respond as vigorously to B. burgdorferi as T cells from normal adult peripheral blood. A large panel of CD4+ T cell clones has been derived that are specific for B. burgdorferi. The majority of these clones are reactive to B. burgdorferi in the presence only of autologous HLA-DR molecules. Collectively, these data suggest that the T cell response from normal individuals is more likely due to multiple antigenic epitopes within Borrelial proteins than a superantigen response.
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PMID:Prominent T lymphocyte response to Borrelia burgdorferi from peripheral blood of unexposed donors. 790 15

Tick-borne pathogens would appear to be vulnerable to vertebrate host immune responses during the protracted duration of feeding required by their vectors. However, tick salivary components deposited during feeding may inhibit hemostasis and induce immunosuppression. The mode of action and the nature of immunosuppressive salivary components remains poorly described. We determined that saliva from the main vector of the agent of Lyme disease, Ixodes dammini, profoundly inhibited splenic T cell proliferation in response to stimulation with concanavalin A or phytohemagglutin, in a dose-dependent manner. In addition, interleukin 2 secretion by the T cells was markedly diminished by saliva. Tick saliva also profoundly suppressed nitric oxide production by macrophages stimulated with lipopolysaccharide. Finally, we analyzed the molecular basis for the immunosuppressive effects of saliva and discovered that the molecule in saliva responsible for our observations was not PGE2, as hypothesized by others, but rather, was a protein of 5,000 mol wt or higher.
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PMID:Saliva of the Lyme disease vector, Ixodes dammini, blocks cell activation by a nonprostaglandin E2-dependent mechanism. 806 26


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