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)

We have previously reported that lipopolysaccharide (LPS) could induce the production of interleukin-3 (IL-3) by mouse spleen cells. In the present study, we show that recombinant human interleukin-1, in the absence of other stimuli, is able to induce the production of IL-3. IL-3 was detected in the supernatants of adult, although neither in young nor in nude mouse splenocytes and was assessed by its capacity to support the growth of the IL-3-dependent FDC-P2 cell line. The presence of IL-3 was antigenically confirmed with a monoclonal anti-IL-3 antibody. Both recombinant IL-1 alpha and IL-1 beta had similar potential for inducing IL-3 production. IL-3 activity was detected in the supernatants of cells cultured in the presence of 100 pg/ml IL-1; maximal IL-3 levels were obtained with 10-30 ng/ml IL-1. Kinetic studies of IL-1-induced IL-3 production indicated that 4-6 days of culture were required for optimal production, whereas 1-2 days were sufficient in cultures stimulated with concanavalin A. Recombinant IL-6 failed to induce significant amounts of IL-3, and TNF alpha induced only weak IL-3 production. GM-CSF but not M-CSF could lead to the appearance of IL-3 in spleen cell culture supernatants. Removal of macrophages decreased the production of IL-3 induced by LPS and GMF-CSF though did not affect the IL-3 production induced by IL-1. This observation suggests that IL-1 production might be an intermediate event in IL-3 production induced by LPS and GM-CSF through the activation of macrophages. IL-3 was detected in culture supernatants of B-cell-depleted splenocytes indicating that T-cells were the source of IL-3. Surprisingly T-cell-depleted populations could also produce IL-3 upon IL-1 stimulation. Preliminary experiments with an autoreactive CD4- CD8- V beta 8+ clone suggested that these cells might also be involved in the described IL-3 production.
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PMID:Induction of interleukin-3 by interleukin-1 in the absence of other exogenous stimuli. 236 39

Leukotrienes (LT), mainly LTB4, have been shown recently to affect several functions of human lymphocytes in vitro, and they are regarded as putative modulators of the immune response. Although it is recognized that human neutrophils, eosinophils, monocyte-macrophages, and mast cells can generate LTs, the synthesis of 5-lipoxygenase products by lymphocytes is still the subject of a controversy. Human peripheral blood mononuclear leukocytes, nylon wool-purified lymphocytes, CD4+, CD4- T cells, large granular lymphocytes, and various fractions of pure lymphocyte preparations obtained by counter flow centrifugal elutriation were stimulated for 10 min to 24 hr with ionophore A23187, phytohemagglutinin, concanavalin A, or lipopolysaccharide with or without exogenous arachidonic acid (AA); supernatants were analyzed by reverse-phase high performance liquid chromatography (HPLC) coupled with radioimmunoassay (RIA) methods for the presence of LTB4. Pure human lymphocyte preparations, which were shown to be free of monocytes, did not release any detectable amount of LTB4. Increasing percentage of contaminating monocytes was clearly paralleled by increasing amounts of LTB4. Murine thymocytes, interleukin 2-dependent CTLL2 cytotoxic lymphocytes, EL4 thymoma cells, and human Jurkatt cells were also found to be unable to generate detectable amounts of LTB4 after stimulation with ionophore A23187, phytohemagglutinin, phorbol myristate acetate, recombinant interleukin 1, or interleukin 2 with or without exogenous AA. The addition of increasing numbers of adherence-purified monocytes to Jurkatt cells was followed by increased synthesis of LTB4. In conclusion, the present study indicates that the synthesis of LTB4 by pure human lymphocyte preparations or some human and animal lymphoid cell lines is not detectable by combined HPLC-RIA methods in any of the conditions used.
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PMID:Assessment of leukotriene B4 synthesis in human lymphocytes by using high performance liquid chromatography and radioimmunoassay methods. 303

Prostaglandin E2 is observed at elevated levels during human immunodeficiency virus (HIV) infection and thus may contribute to the HIV-dependent immunosuppression. The mechanisms responsible for this increase are not understood. Evidence indicates that the viral envelope proteins perturb membrane signaling mediated by the CD4 receptor, suggesting that the free envelope protein and/or the intact virus may be responsible for the increase in prostaglandin E2 levels. In this study, we have used THP-1 human monocytes and THP-1 cells differentiated by 12-O-tetradecanoylphorbol-13-acetate treatment into macrophages to determine if the HIV envelope protein, gp120, or an anti-CD4 receptor antibody stimulates prostaglandin formation by interacting with the CD4 receptor. Incubation of THP-1 cells with OKT4A antibody greatly stimulated the CD4-p56lck receptor complex as estimated by enhanced p56lck autophosphorylation, while the gp120 gave small but significant responses. Monocytic THP-1 cells poorly metabolized arachidonic acid to prostaglandin E2 and thromboxane B2 as measured by high-pressure liquid chromatography analysis. Western blot (immunoblot) and Northern (RNA) blot analyses revealed that unstimulated monocytes expressed little prostaglandin H synthase 1 and 2 (PGHS-1 and -2). Incubation of the monocytes with lipopolysaccharide, OKT4A, or gp120 did not increase the formation of prostaglandins. The expression of PGHS-1 or PGHS-2 was also not increased. Differentiation of the monocytes to macrophages by 12-O-tetradecanoylphorbol-13-acetate treatment resulted in increased expression of PGHS-1 and increased formation of prostaglandins compared with that for the monocytes. Lipopolysaccharide stimulation of the macrophages increased the formation of prostaglandins and increased the expression of PGHS-2 in the macrophages. However, OKT4A or gp120 preparation, at concentrations that stimulated p56lck autophosphorylation, did not enhance the formation of prostaglandins or the expression of PGHS-1 or PGHS-2. OKT4A and gp120 also did not stimulate the release of arachidonic acid, indicating that phospholipase A2 was not activated by the CD4 receptor in either the THP-1 monocytes or macrophages. These results indicate that activation of the CD4-p56lck receptor signal transduction pathway by the HIV envelope protein does not increase prostaglandin formation.
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PMID:Human immunodeficiency virus type 1 envelope protein does not stimulate either prostaglandin formation or the expression of prostaglandin H synthase in THP-1 human monocytes/macrophages. 749 15

Microglial cell lines from rat brain were established by transfer of a temperature sensitive simian virus 40 large tumour antigen by means of a retrovirus. Four weeks after infection, colonies were generated in the presence of neomycin and granulocyte-macrophage colony stimulating factor (GM-CSF), and subsequently subcloned. Both bulk cell lines and clones proliferate actively at 33 degrees C, whereas the rate of division was significantly decreased at 39 degrees C when the large T antigen is non-functional. At 39 degrees C, these cells take on the microglial phenotype as demonstrated by immunoreactivity to ED-1 (an intracellular antigen), OX-42 (complement type 3 receptor), W3/25 (CD4 homologue), OX-6 (MHC class II antigen) and OX-18 (MHC class I antigen). These cells are capable of active phagocytosis and retain these properties for 10-15 passages. Long-term culture of these lines and clones, greater than 15 passages, displayed a gradual down-regulation of all cell surface specific antigens that were not rescued by lipopolysaccharide (LPS), interferon-gamma (gamma-IFN), GM-CSF or colony-stimulating factor-1 (CSF-1). The expression of the SV-40 large T antigen was unaffected. These results demonstrate the feasibility of immortalizing short-term cell lines with the SV-40 large T antigen for their use in the characterization of microglial properties.
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PMID:Immortalization and characterization of rat microglial cells. 749 98

We investigated the effect of intratracheal (i.t.) lipopolysaccharide (LPS) on alveolar macrophage release of nitric oxide. Mice received i.t. LPS at doses ranging from 1 to 100 micrograms/100 g body weight and were killed at serial intervals for bronchoalveolar lavage. Control mice received i.t. phosphate-buffered saline. We found that after i.t. LPS, there was an early (1 to 3 days) influx of neutrophils followed by a later (5 to 7 days) influx of macrophages into the lungs. Alveolar macrophages lavaged from mice given i.t. LPS did not spontaneously release nitric oxide (measured as nitrite), but the capacity of these cells to release nitric oxide in vitro in response to interferon-gamma (IFN-gamma) or LPS was markedly upregulated. Alveolar macrophages lavaged from mice given i.t. LPS but not i.t. phosphate-buffered saline also expressed mRNA for inducible nitric oxide synthase as measured by semiquantitative reverse-transcription polymerase chain reaction. To investigate possible mechanisms for cellular priming for increased nitric oxide release after i.t. LPS, mice were depleted of CD4+ lymphocytes with an anti-CD4 antibody. Alveolar macrophages from CD4-depleted mice given i.t. LPS released significantly less nitric oxide in vitro in comparison to macrophages from nondepleted mice. Additional mice were treated with neutralizing doses of anti-tumor necrosis factor or anti-IFN-gamma antibody before i.t. LPS. Pretreatment with each cytokine antibody decreased but did not eliminate macrophage priming for nitric oxide release after i.t. LPS. We conclude that intratracheal LPS induces mRNA for nitric oxide synthase in alveolar macrophages, priming the cells for increased release of nitric oxide in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of nitric oxide release by macrophages after intratracheal lipopolysaccharide. 754 Dec 22

The mechanisms by which regulatory CD4- CD8+ suppressor T cells (Ts) and CD4+ CD8- amplifier T cells (Ta) influence the magnitude of the antibody response to the capsular polysaccharide antigen of type III Streptococcus pneumoniae are reviewed in detail. This represents the best-characterized experimental model system available for demonstrating how subsets of T cells act in a negative and positive manner to control the magnitude of an antibody response. The fact that transferred Ts and Ta elicit their effects in athymic immunized mice affirms, that such regulatory T cells are antigen-specific and act on immune B cells to produce the effects observed. The ability of the lipid A and the inner core-region oligosaccharide fractions of bacterial lipopolysaccharide to abolish and increase the expression of Ts function, respectively, is examined with respect to its immunomodulatory potential and its possible role in enhancing the virulence of Gram-negative bacteria.
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PMID:T-cell mediated immunosuppression and its implications for the development of protective immunity. 758 94

Implantation of pellets containing 75 mg of morphine induced short term (4 day) morphine dependence and markedly reduced total number of spleen cells of BALB/c mice, without affecting total body or liver weight. Polyclonal responses induced by anti-CD3 antibodies, Concanavalin A or Escherichia coli lipopolysaccharide in the remaining spleen cells of morphine-treated mice were also inhibited. Cytofluorimetric analysis indicated that the proportion of major functional lymphocyte populations (Ig+, CD3+, CD4+ and CD8+ lymphocytes) were not significantly changed in the spleen from morphine-dependent mice. Furthermore, expression levels of surface Ig, CD3, CD4, and CD8, were similar in spleen cells from control or morphine-treated mice. So, morphine dependence in BALB/c mice under these controlled conditions results in a specific defect in lymphoid cell number and function, with no incidence on body weight or particular lymphocyte subsets.
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PMID:Suppression of immune parameters in animal models of morphine dependence. 762

Mechanisms underlying the control of cytokine secretion by alveolar macrophages are not fully understood. We hypothesized that T lymphocytes or their products modulate the capacity of alveolar macrophages to release cytokines in response to an exogenous stimulus. In this study, we investigated the role of lymphocytes expressing surface CD4 (CD4+) antigen in the regulation of tumor necrosis factor alpha (TNF-alpha) secretion by alveolar macrophages. Specific pathogen-free male BALB/c mice were injected intraperitoneally with 0.3 mg monoclonal anti-CD4 antibody or phosphate-buffered saline. Depletion of CD4+ splenic lymphocytes was confirmed 6 days later by flow cytometry. On day 6, mice were challenged intratracheally with E. coli lipopolysaccharide (LPS, 1-100 micrograms/100 g BW) or phosphate-buffered saline. The lungs were lavaged 3 h later and the bronchoalveolar lavage fluid assessed for TNF activity and cell recovery (total and differential). No TNF was detected in the lavage fluid of animals pretreated with antibody or phosphate-buffered saline and given phosphate-buffered saline intratracheally. However, the saline-treated mice challenged with LPS (100 micrograms/100 g BW) released 3.76 +/- 0.18 ng TNF/ml bronchoalveolar lavage fluid. In contrast, mice depleted of CD4+ T lymphocytes released almost 50% less TNF (1.94 +/- 0.23 ng TNF/ml lavage fluid, p < 0.001) in response to the same dose of LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CD4+ T lymphocyte depletion attenuates lipopolysaccharide-induced tumor necrosis factor secretion by alveolar macrophages in the mouse. 770 9

We have previously reported that MH-S, an established murine alveolar macrophage-derived cell line, mediated profound inhibition of in vitro antibody production, as did their freshly isolated alveolar macrophage (AM) counterparts. In this communication we show that like freshly recovered AMs, the MH-S cell line also displays phenotypic and functional heterogeneity. Sorting of parental MH-S cells by flow cytometry based on reactivity with anti-Mac-1 antibody yielded two subsets. Further analysis by staining with monoclonal antibodies against well-characterized murine macrophage cell surface markers revealed that both Mac-1+ and Mac-1- subsets expressed the mature murine macrophage antigen (F4/80) and class II major histocompatibility complex molecules, but with different intensity. In contrast, the two subsets stained equivalently with antibody against the Fc gamma II receptor, whereas neither subset stained with anti-CD4 antibody. Examination by light microscopy revealed plemorphism in the Mac-1+ population with many of the cells appearing spindle shaped and having elongated processes, whereas a majority of the cells in the Mac-1- population were spherical in shape. Functionally, cells from the Mac-1+ population were less inhibitory of in vitro antibody production and produced significantly more nitric oxide in response to stimulation with lipopolysaccharide than were cells in the Mac-1- population. Essentially similar results were obtained using cloned Mac-1+ and Mac-1- MH-S cells. The finding of heterogeneity in an established cell line that displays functions similar to those of freshly recovered AMs suggests that distinct subsets of AMs may be involved in the pathogenesis of disease processes in the lung.
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PMID:Phenotypic and functional heterogeneity of the murine alveolar macrophage-derived cell line MH-S. 772 15

Pharmacological evidence indicates that lymphocytes express opioid receptors, but this finding has been questioned. By DNA sequencing of reverse transcription-polymerase chain reaction products, we have found that mouse lymphocytes express mRNA encoding an orphan opioid receptor. These mRNA transcripts were detected in the CD4+, CD8+, and CD4- CD8- lymphocyte subpopulations. Northern blot analysis confirmed that splenic lymphocytes express a 1.5-kb orphan opioid receptor mRNA. Fifteen bases encoding Tyr71-Arg75 in the first intracellular loop are alternatively spliced, suggesting that orphan opioid receptor mRNA encodes two receptor subtypes. Treatment of lipopolysaccharide-stimulated lymphocytes with orphan opioid receptor antisense oligonucleotides suppressed polyclonal IgG and IgM production by 50%. Our results provide direct evidence that lymphocytes express an opioid-like receptor gene, and suggest that this receptor plays a functional role in immunocompetence.
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PMID:Functional role and sequence analysis of a lymphocyte orphan opioid receptor. 779 25


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