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)

Five known complement activators were evaluated for their capacity to directly activate murine macrophages and to trigger activation of lymphokine primed macrophages for nonspecific tumor cytotoxicity. Bacterial lipopolysaccharide (LPS), Lipid A, polyinosinic-polycytidylic acid, cobra venom factor (CVF), and zymosan directly activated macrophages in a dose-dependent fashion at high concentrations. Subactivating concentrations of each of these agents were found to effectively trigger macrophages which were preprimed either by macrophage-activating factor or by murine recombinant interferon gamma for enhanced tumoricidal activity. An Fc receptor blockade with opsonized sheep erythrocytes abrogated LPS-mediated direct activation and triggering of interferon gamma-primed macrophages, but had no inhibitory effect on direct activation or triggering by CVF for nonspecific tumor cytotoxicity. This study characterizes the capacity of a diverse group of known complement activators to serve as second signal triggers for culmination of the activation process of interferon-primed macrophages for nonspecific tumoricidal activity. These findings suggest that complement activators may directly activate macrophages by stimulation of interferon beta production by macrophages for self-priming and, as we have shown, act as self-triggers. The putative role of macrophage-associated complement components in the activation process is discussed.
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PMID:Triggering of interferon gamma-primed macrophages by various known complement activators for nonspecific tumor cytotoxicity. 310 95

The dye fura-2, a potentially more sensitive successor to quin2 for measuring intracellular free calcium ion concentrations [(Ca2+]i), has been applied here to investigate the possible involvement of early changes in [Ca2+]i in the stimulation of the human monocyte-macrophage-like cell line U937. The calcium ionophores A23187 and ionomycin, known pharmacological stimuli for macrophages, were found to cause sharp rises in [Ca2+]i as expected. Responses analogous to those reported for a murine macrophage cell (J774) were obtained on stimulation of U937 cells with ATP which caused rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 200 mM). In addition to ATP, several agents known to activate macrophages were used as stimuli. In particular, platelet-activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was found to cause rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 400 nM) even at concentrations as low as 10(-10) M. This contrasts with responses to ATP that were markedly reduced at 10(-6) M compared with 10(-5) M or above, suggesting that PAF is a highly potent stimulus for intracellular calcium mobilization in macrophages. Similar responses were obtained with chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine). On the other hand, two agents known to be potent activators of macrophages, interferon gamma and lipopolysaccharide, had no rapid effect on [Ca2+]i. This may reflect differences in the kinetics of signal-response coupling or alternatively a different mechanism of action by-passing the need for rapid elevation of [Ca2+]i.
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PMID:Rapid intracellular calcium changes in U937 monocyte cell line: transient increases in response to platelet-activating factor and chemotactic peptide but not interferon-gamma or lipopolysaccharide. 311 54

Macrophages play a crucial role in the defense against tumors and parasites. Activation of tumoricidal and microbicidal effector mechanisms requires stimulation of macrophages with macrophage-activating factors (MAF). One such MAF is interferon gamma (IFN-gamma). In some assays, substantial activity of IFN-gamma on murine macrophages, however, is only observed in synergy with lipopolysaccharide (LPS) or other cytokines (1). In addition, certain cytokines have been shown to induce monocyte or macrophage activation in the absence of IFN-gamma (2-5). We previously described lymphokines in the supernatant of a murine T cell clone that synergized with IFN-gamma in the induction of tumoricidal and schistosomulicidal murine macrophages (1). We called this lymphokine(s) macrophage cytotoxicityinducing factor 2 (MCIF2)(1). A candidate for MCIF2 was lymphotoxin (LT), because the T cell clone supernatant contained high amounts of LT. LT is functionally homologous and structurally related to the macrophage product tumor necrosis factor (TNF). Therefore, we tested whether recombinant (r) LT or rTNF can function as MAF. We report here that rLT or rTNF synergize with rIFN-gamma in the induction of tumoricidal and schistosomulicidal murine macrophages.
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PMID:Interferon gamma and lymphotoxin or tumor necrosis factor act synergistically to induce macrophage killing of tumor cells and schistosomula of Schistosoma mansoni. 311 Mar 55

Human T cell hybridoma, H3-E9-6, that produces macrophage activating factors for cytotoxicity (MAF-C) was prepared by somatic fusion of phytohemagglutinin-activated peripheral blood lymphocytes with emetine/actinomycin D-treated cloned human acute lymphocytic leukemia cells (CEM 11). The activities of the following were assayed: (1) macrophage-activating factor for cytotoxicity of monocytes (MAF-C 1 day), (2) macrophage-activating factor for cytotoxicity of monocyte-derived macrophages (MAF-C 6 day), (3) macrophage-activating factor for cytotoxicity of murine macrophages (MAF-Cm), (4) macrophage-activating factor for glucose consumption (MAF-G), (5) macrophage-activating factor for O2- formation (MAF-O). The culture supernatant of H3-E9-6 showed MAF-C 1 day-MAF-C 6 day, MAF-Cm, and MAF-G activities. The MAF-Cm activity was considerably enhanced by the addition of murine recombinant interferon gamma (rIFN-gamma). The MAF-C 1 day activity in the H3-E9-6 sup was not decreased by heat treatment (56 C, 30 min), by pH 2 treatment or by the addition of monoclonal anti-human IFN-gamma antibody or polymyxin B. These data suggest that MAF-C in H3-E9-6 sup is distinct from human IFN-gamma or lipopolysaccharide (LPS).
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PMID:Human macrophage-activating factors for cytotoxicity. I. Establishment of a human T-cell hybridoma that produces macrophage-activating factors for cytotoxicity. 311 71

Two different factors (MAF-C I and MAF-C II) were obtained by anion exchange chromatography of the culture supernatant of a human T-cell hybridoma, H3-E9-6, which produces macrophage-activating factors for cytotoxicity (MAF-C). These 2 factors induced the cytotoxicity of monocytes synergistically as a priming signal (MAF-C I) and a triggering signal (MAF-C II), respectively. On gel filtration on a column of Superose 12, MAF-C II was eluted mainly at the void volume, whereas MAF-C I was eluted in the fractions corresponding to approximate molecular weights of 30-300 K. On the other hand, gel filtration in the presence of sodium deoxycholate revealed that MAF-C II has an approximate molecular weight of 40,000, but MAF-C I was unstable under these conditions. When the activity for mouse macrophages (MAF-Cm activity) was tested, the MAF-C II fraction showed high MAF-Cm activity in the presence of murine recombinant interferon gamma (rIFN-gamma), but the MAF-C I fraction did not show MAF-Cm activity even in the presence of lipopolysaccharide (LPS). These results suggest that MAF-C I (priming lymphokine) has species specificity but MAF-C II (triggering lymphokine) does not.
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PMID:Human macrophage-activating factors for cytotoxicity. II. Synergism of two factors produced by a human T-cell hybridoma that induce the cytotoxicity of human monocytes. 311 72

Experiments have been carried out to assess the ability of purified protein-free lipopolysaccharide (LPS) and lipid A-associated protein (LAP) containing LPS to activate macrophages from C3H/HeJ endotoxin-unresponsive mice. Assays for in vitro activation have included cytotoxic and cytostatic effects on a simian virus 40 (SV40)-transformed fibroblast cell line. While neither preparation of LPS would effect C3H/HeJ macrophage activation for either cytostasis or cytolysis, the addition of murine interferon gamma to cultures of LAP-LPS stimulated C3H/HeJ macrophages resulted in cells which were both cytotoxic and cytostatic. These results suggest that LAP can provide one component of the triggering mechanism but, of itself, is insufficient to effect full activation. A second signal, which can be provided by murine interferon gamma, appears also to be required.
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PMID:Tumor cell killing and cytostasis by C3H/HeJ macrophages activated in vitro by lipid A-associated protein and interferon gamma. 312 94

Unique hybrids (HINS and CANS lines) between macrophages and a myeloma cell line, NS1 initially expressed myeloma functions but later expressed active macrophage functions together with constitutive expression of c-fos gene. Enhancement of c-fos transcription was also observed in activated mouse peritoneal macrophages, and a range of macrophage-stimulating substance was found to induce c-fos transcription kinetic unique to each stimulator including immediate, delayed and prolonged responses in aged HINS-B3 cells, which displayed low levels of steady-state c-fos transcription. It was also found that a significant enhancement of c-fos transcription followed restimulation with either interferon gamma (IFN gamma) or lipopolysaccharide (LPS) after an initial IFN gamma stimulation. Thus it appeared that enhanced c-fos expression was closely connected with macrophage activation. On the other hand, macrophage stimulators suppressed [3H]thymidine incorporation into aged HINS-B3 cells. These results may simply suggest that c-fos expression contributes to macrophase activation but not to cell proliferation. However, it is also possible to speculate that c-fos expression contributes to cell proliferation as a salvage system operating to overcome the suppression during the macrophage activation.
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PMID:Enhancement of c-fos expression is associated with activated macrophages. 313 20

The human myelomonocytic cell line RC2a expressed procoagulant activity following stimulation with human lymphokine (LK) prepared by stimulating peripheral blood mononuclear cells with either mitogens (Concanavalin A, phytohaemagglutinin or antigen (tuberculin). Induction was rapid, with optimal activity observed between 6 and 8 h, was decreased in cultures containing serum and was not inhibited by actinomycin D or cycloheximide. The LK activity was not inhibited by an anti-interferon gamma (IFN gamma) antibody. IFN gamma and phorbol myristate acetate (PMA) had no activity but acted in synergy to induce procoagulant expression; interferon alpha plus PMA were without effect. In contrast to the LK-induced response, procoagulant induced by IFN gamma/PMA was not detected for up to 8 h and steadily rose over 24-48 h culture and was dependent on new protein and RNA synthesis. Bacterial lipopolysaccharide, a potent inducer of thromboplastin on normal human monocytes, failed, either alone or in combination with LK, IFN gamma, PMA or IFN gamma plus PMA, to activate procoagulant expression on RC2a cells. Both LK and IFN gamma/PMA-induced procoagulant had properties of thromboplastin expressed both intracellularly and on intact, viable cells. This study shows that RC2a cells are responsive to factors produced as the result of an activated cell-mediated immune response which may therefore contribute to the coagulopathies common to this form of malignancy.
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PMID:Procoagulant induction by human lymphokine and interferon gamma/PMA on a myelomonocytic cell line, RC2a. 314 14

Previous studies have shown that murine macrophages immunostimulated with interferon gamma and Escherichia coli lipopolysaccharide synthesize NO2-, NO3-, and citrulline from L-arginine by oxidation of one of the two chemically equivalent guanido nitrogens. The enzymatic activity for this very unusual reaction was found in the 100,000g supernatant isolated from activated RAW 264.7 cells and was totally absent in unstimulated cells. This activity requires NADPH and L-arginine and is enhanced by Mg2+. When the subcellular fraction containing the enzyme activity was incubated with L-arginine, NADPH, and Mg2+, the formation of nitric oxide was observed. Nitric oxide formation was dependent on the presence of L-arginine and NADPH and was inhibited by the NO2-/NO3- synthesis inhibitor NG-monomethyl-L-arginine. Furthermore, when incubated with L-[guanido-15N2]arginine, the nitric oxide was 15N-labeled. The results show that nitric oxide is an intermediate in the L-arginine to NO2-, NO3-, and citrulline pathway. L-Arginine is required for the activation of macrophages to the bactericidal/tumoricidal state and suggests that nitric oxide is serving as an intracellular signal for this activation process in a manner similar to that very recently observed in endothelial cells, where nitric oxide leads to vascular smooth muscle relaxation [Palmer, R. M. J., Ashton, D. S., & Moncada, S. (1988) Nature (London) 333, 664-666].
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PMID:Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. 324

The polypeptide interleukin-1 (IL-1) is a cytokine that may mediate inflammation and connective tissue damage in rheumatoid arthritis (RA). We examined cytokine production by normal blood and by rheumatoid synovial mononuclear cells with sensitive (picomolar) assays. The assays were immunolabeling and immunoblotting with rabbit anti-IL-1 beta sera, and proliferation of the murine D10 cell line to IL-1. Little or no cytokine was detected in rheumatoid joint fluid or in exudate mononuclear cells from patients with acute rheumatoid flares. The mononuclear cells could be induced to make IL-1 upon stimulation with lipopolysaccharide (LPS). The responsive cells were monocytes, since all could be double-labeled with anti-IL-1 and the monocyte-specific CD14 antibody. More than 80% of the synovial fluid monocytes made IL-1 beta after 24 hr in 2 ng/ml LPS. Other agents failed to induce IL-1 from enriched populations of monocytes including interferon gamma (IFN-gamma), poly (I/C), phorbol myristate acetate (PMA), concanavalin A (Con A), phytohemagglutinin (PHA), and anti-CD3 antibodies. Relatively high levels of dendritic cells (DC) were present in RA effusions, but these did not produce IL-1 in response to any of the above stimuli. Blood dendritic cells also did not make IL-1, whereas blood monocytes responded comparably to synovial exudate cells. The data indicate that rheumatoid exudate monocytes make very little IL-1 during acute flares of arthritis and that this cytokine is primarily a macrophage rather than a dendritic cell product.
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PMID:Interleukin-1 production by mononuclear cells from rheumatoid synovial effusions. 326 May 44


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