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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of murine peritoneal macrophages for 30 min with lipopolysaccharide (LPS) resulted in a transient increase in c-fos proto-oncogene mRNA levels (Introna et al., 1986). After 2 h from the initial treatment, c-fos mRNA could no longer be detected and its expression could not be restimulated either by LPS or by other signals including colony stimulating factor-1 (CSF-1) and phorbol myristate acetate (PMA), both of which are able to induce expression of the c-fos gene in unstimulated macrophages. When LPS was removed after an initial 30 min incubation, responsiveness to a second exposure to LPS began to reappear after 3 h and was completely restored by 20 h. The same pattern of desensitization of c-fos induction was observed when CSF-1 stimulated macrophages were subsequently exposed to LPS. The loss of sensitivity to PMA following pretreatment with LPS was selective for c-fos expression as LPS treated macrophages remained responsive to PMA with respect to the ability to stimulate secretion of H2O2. The mechanism of desensitization was localized, at least in part, at the level of transcription as demonstrated by analysis of c-fos transcripts in nuclei isolated from macrophages pretreated and restimulated with LPS.
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PMID:Homologous and heterologous desensitization of proto-oncogene cfos expression in murine peritoneal macrophages. 357 35

Expression of cellular cytotoxicity by monocytes or macrophages has been conceived as an induced function secondary to collaboration in the immune response or to other agonists. However, a form of spontaneous cellular cytotoxicity by monocytes analyzed with unseparated human peripheral blood mononuclear cells (PBM) has been described by using the 6-hr 51Cr release from actinomycin D (ActD)-treated murine WEHI 164 cells, a target cell refractory to the cytotoxic effects of natural killer and cytolytic T cells. We observe that when cells are isolated under rigorously endotoxin-free conditions, there is no cytotoxicity. Inclusion of serum does not induce cellular cytotoxicity; however, cytotoxic activity is induced by the presence of as little as 1 pg/ml of bacterial lipopolysaccharide (LPS). PBM required 2 hr of preexposure to endotoxin in order to express full cytotoxic activity. We investigated the basis of the cytotoxicity of WEHI 164 cells and the effect of ActD. ActD-treated target cells are highly susceptible to the effects of TNF-alpha and TNF-beta (alpha-lymphotoxin), whereas untreated target cells were resistant. In contrast, ActD does not affect susceptibility to the cytotoxic effects of H2O2, and interleukin 1 is not cytotoxic to the target cells. With the use of a neutralizing monoclonal antibody specific for TNF-alpha, the cytotoxic activity induced by LPS greatly diminished and the amount of TNF-alpha neutralized is similar to that required for equivalent cytotoxicity. We conclude that monocytes present in human PBM are not "spontaneously" cytotoxic for ActD-treated WEHI 164 target cells, but that the reported cytotoxicity results from exposure to a level of endotoxin or endotoxin-like agonists to which the cells are exposed. The cytotoxicity is mediated mostly if not entirely by TNF-alpha, an established product of monocytes/macrophages. With the use of endotoxin-free conditions, PBM can be isolated in a cytotoxically latent state, suitable for analysis of the immunologic regulation of TNF-alpha-mediated monocyte cellular cytotoxicity.
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PMID:Tumor necrosis factor production by human monocytes is a regulated event: induction of TNF-alpha-mediated cellular cytotoxicity by endotoxin. 376 May 68

We have previously reported a diminution of protein synthesis by isolated Sprague-Dawley rat hepatocytes following coculture with lipopolysaccharide-triggered nonparenchymal liver cells (NPC) containing 30-40% Kupffer cells. It is possible that this cell-mediated modulation of hepatocyte function represents an in vitro model for hepatic insufficiency occurring in patients with the multiple system organ failure syndrome. In the present report we have determined that supernatant from lipopolysaccharide-triggered NPC was itself capable of inhibiting hepatocyte protein synthesis in a similar fashion. This effect was directly related to the concentration of the supernatant and to the period of exposure to the supernatant. The ability to inhibit hepatocyte protein synthesis by a NPC supernatant suggests that this cell-mediated event is caused at least in part by a relatively stable soluble factor(s) secreted by LPS triggered NPC. Although reagent H2O2 will inhibit protein synthesis when added to hepatocyte culture, LPS-stimulated NPC do not release H2O2 and do not show chemiluminescence--an in vitro correlate of the respiratory burst. Nonspecific protease inhibitors added to the coculture similarly do not influence the system. Combined with other evidence, the soluble mediators do not seem to be the result of oxidative or proteolytic secretions of the effector cells.
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PMID:Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells. II. Mediation by soluble transferrable factors. 388 24

The effect of bacterial lipopolysaccharide on the Fc-receptor-mediated respiratory burst in murine peritoneal macrophages has been examined. After treatment overnight with small quantities of LPS, macrophages exhibited dramatic diminution of their capacity to generate and secrete H2O2 when triggered with immune complexes. The effect of LPS treatment was dependent on the state of macrophage functional activation; only cells that were primed or fully activated in vivo or were treated with interferon-gamma in vitro were sensitive to this effect of LPS. The LPS-mediated loss of secretory function was both dose and time dependent and could be reproduced with the lipid A moiety of LPS. The effect was selective for H2O2 secretion triggered through the Fc receptor; the respiratory burst stimulated by phorbol diesters remained unaltered. Furthermore, LPS treatment did not alter either binding or ingestion of radiolabeled immune complexes in parallel with the change in H2O2 secretion, indicating that the suppressive effect was not due to compromised endocytic function. These results indicate that LPS treatment of primed macrophages regulates the function of Fc receptors and may uncouple receptor occupancy from generation and secretion of H2O2.
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PMID:Regulation of the Fc-receptor-mediated respiratory burst: treatment of primed murine peritoneal macrophages with lipopolysaccharide selectively inhibits H2O2 secretion stimulated by immune complexes. 399 71

We investigated the capacity of bacterial endotoxin (lipopolysaccharide, LPS) to modify the oxidative metabolic response to membrane stimulation of human neutrophils. Neutrophils were pretreated for 60 min with LPS, 10 ng/ml, then stimulated by exposure to fixed immune complexes, the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP), or phorbol myristate acetate. Release of superoxide anion (O-2) was up to 7-times greater in cells preincubated with LPS, depending upon the stimulus used. Consumption of oxygen and release of hydrogen peroxide (H2O2) were similarly increased, using FMLP as stimulus. The enhancement was accompanied by a reduction in lag time and an increase in the rate of the response, but the duration of the oxidative events was not changed. The molecular basis for the augmented oxidative response of LPS-pretreated cells was investigated. Preincubation with LPS at 0 degrees C prevented priming, but preincubation in the presence of cycloheximide or chelation of extracellular calcium ion did not. Neutrophils preincubated with LPS had slightly decreased numbers of binding sites and equivalent binding affinity for radiolabeled FMLP. Possible changes in the enzyme responsible for the oxidative burst were analyzed by studying NADPH-dependent generation of O-2 by particulate fractions from cells preincubated with LPS or buffer, then stimulated before cell disruption. The fraction prepared from LPS-pretreated neutrophils exhibited greater release of O-2 over a wide range of concentrations of NADPH. The calculated apparent Km for NADPH was equivalent in the two fractions, but the Vmax was increased 2.5-fold in the subcellular fraction from LPS-pretreated cells. These results suggest that LPS could increase neutrophil-mediated host defense or the tissue damage associated with endotoxemia by enhancing the generation of oxygen metabolites by neutrophils. These results also support the concept that the neutrophil is not an end-stage cell in regard to function or metabolic activity.
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PMID:Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipopolysaccharide. Evidence for increased activity of the superoxide-producing enzyme. 609 75

The data reported in this paper are the first demonstration that different T cell clones (PC-AKR-CI 96, clone 96; PK 7.1.2 E8, clone 7.1.2 E8) secrete different macrophage-activating factors (MAF) that induce distinct macrophage activities. Incubation of resident murine macrophages with MAF 7.1.2 E8 increased RNA, protein, and glycoprotein synthesis, hexosemonophosphate shunt (HMPS) activity, release of oxygen metabolites (O-2, H2O2), pinocytosis, phagocytosis, and tumor cytostasis, whereas no effect on prostaglandin E (PGE) release, schistosomula killing, and tumor cytolysis could be observed. In contrast, MAF 96 increased glycoprotein synthesis, HMPS activity, release of oxygen metabolites and PGE, schistosomula killing, and tumor cytostasis and cytolysis, whereas RNA and protein synthesis and pinocytosis were decreased and phagocytosis remained unaffected. Thus, MAF from both T cell clones share some macrophage-activating properties but differ in others. Most importantly, both MAF could be differentiated serologically by a rabbit anti-lymphokine antiserum that selectively inhibited MAF 96 but not MAF 7.1.2 E8 activity. At optimal concentrations, MAF 96 and 7.1.2 E8 were active in the absence of lipopolysaccharide (LPS) whereas LPS enhanced the activity of suboptimal doses of MAF 96 but not of MAF 7.1.2 E8. These data are discussed with respect to the possibility that the functional dichotomy of T cell clones might reflect different activities of normal T cell subpopulations.
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PMID:Macrophage-activating factors from different T cell clones induce distinct macrophage functions. 619 Sep 40

We have observed that the synthesis and secretion of apo-E, a component of plasma lipoproteins, are suppressed in mouse macrophages exposed to bacterial lipopolysaccharide endotoxin (LPS) in culture or in vivo. Control mouse macrophages contained intracellular immunofluorescent apo-E, and apo-E represented about 10% of secreted protein. After intraperitoneal injection of LPS, freshly lavaged macrophages neither contained intracellular apo-E nor secreted apo-E. The suppressive effects of LPS on apo-E synthesis in culture were selective, and secretion of many other major macrophage proteins was not affected. When the LPS-elicited macrophages were cultured for 24-72 h in the absence of LPS, synthesis of apo-E was initiated. Treatment of bone marrow-derived or peritoneal macrophages in culture with less than 1 ng of LPS/ml inhibited apo-E synthesis and secretion by 18 h of treatment. Although LPS stimulates prostaglandin E2 synthesis, prostaglandin E2 itself did not suppress apo-E synthesis. Macrophages from C3H/HeJ (Lpsd/Lpsd) mice, which are resistant to LPS, were neither primed for H2O2 production nor suppressed for apo-E synthesis in response to LPS in vivo (30 micrograms/mouse) or in culture (1 microgram/ml), whereas macrophages from the co-isogenic C3H/HeN (Lpsn/Lpsn) strain were induced for H2O2 secretion and had suppressed synthesis of apo-E. Because apo-E serves as a recognition determinant for the receptor-mediated clearance of lipoproteins, the decreased synthesis of apo-E after LPS treatment may in part explain the hyperlipoproteinemia associated with endotoxins in vivo.
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PMID:Endotoxin suppresses expression of apoprotein E by mouse macrophages in vivo and in culture. A biochemical and genetic study. 635 Feb 91

The data reported in this paper demonstrate that macrophage-activating factors (MAFs) are a heterogeneous group of T-cell-derived lymphokines. Two long-term T-cell clones, Cl 96 and PK 7.1.2E8, were potent sources of MAFs (MAF96 and MAF7.1.2E8). These MAFs could be distinguished by differential activation of macrophages. Activation of resident murine macrophages with MAF7.1.2E8 enhanced RNA and glycoprotein synthesis, hexosemonophosphate shunt (HMPS) activity, release of oxygen metabolites (O-2 and H2O2), pinocytosis and tumor cytostasis, whereas no effect on schistosomula killing and tumor cytolysis could be observed. In contrast, MAF96 enhanced glycoprotein synthesis, HMPS activity, release of oxygen metabolites and prostaglandin E, schistosomula killing, and tumor cytostasis and cytolysis, while RNA synthesis and pinocytosis were decreased. These findings show that MAFs from both T-cell clones share some properties but markedly differ in others. In addition, the macrophage-activating properties of MAF96 but not of MAF7.1.2E8 could selectively be inhibited by a rabbit anti-lymphokine antiserum. This demonstrates a serological difference between MAF activities from both clones. Although at optimal concns both MAFs were active in the absence of lipopolysaccharide (LPS), the activity of suboptimal doses of MAF96 but not of MAF7.1.2E8 could be enhanced by LPS. These findings show that different MAFs from T-cell clones may be useful to clarify molecular mechanisms of macrophage activation.
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PMID:Activation of macrophages by lymphokines from T-cell clones: evidence for different macrophage-activating factors. 639 5

The cellular sites of H2O2 formation in phagocytizing granulocytes have been identified with cerium chloride. A precipitate was visible in phagosomes and on plasma membranes from intact normal cells in the presence of either 0.71 mM NADH or NADPH. X-ray microanalysis permitted identification of cerium deposition within the phagosomes even in the absence of reduced pyridine nucleotides. Catalase ablated the formation of the reaction product. Intact granulocytes obtained from subjects receiving 1600 units of vitamin E daily for 2 weeks exhibited reaction product in the presence of NADH but not NADPH. Intact cells from subjects treated with vitamin E demonstrated diminished numbers of phagocytic vesicles containing reaction product. During phagocytosis the granulocytes treated with vitamin E consumed oxygen but exhibited significantly reduced rates of hydrogen-peroxide-dependent glucose-1-14C oxidation to 14CO2. Isolated phagocytic vesicles obtained from granulocytes after ingestion of opsonized lipopolysaccharide-paraffin oil droplets contained reaction product when exposed to 0.71 mM NADPH. No reaction product was evident at 0.71 mM NADH but was evident at 2.0 mM NADH. Isolated phagocytic vesicles from the granulocytes of subjects receiving vitamin E exhibited reaction product only in the presence of NADH. These observations suggest that vitamin E interferes with the electron transport chain apparently required for the oxidation of NADPH to form H2O2 in the phagocytizing granulocyte.
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PMID:Vitamin E--a selective inhibitor of the NADPH oxidoreductase enzyme system in human granulocytes. 661 42

Inflammatory cells such as phagocytes, neutrophils, and macrophages have been implicated in the pathogenesis of several forms of clinical and experimental tumor development. It is hypothesized that this process is mediated by the production of reactive species including NO., O2.-, H2O2, and ONOO- which inflict DNA damage. In this study, the role of NO. in combination with oxygen radicals in DNA damage was investigated. DNA deamination (xanthine) and oxidation [5-(hydroxymethyl)uracil (5HMU), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FAPY-G), and 8-oxoguanine (8oxoG)] products were identified in the DNA of macrophages (RAW264.7) activated with Escherichia coli lipopolysaccharide (LPS) and mouse gamma-interferon (INF-gamma). The formation of these products was inhibited by N-methyl-L-arginine (NMA), a nitric oxide synthase inhibitor. NMA inhibited only the production of nitric oxide and had no effect on superoxide production. These results demonstrate that NO. plays a dual role in damaging the DNA of activated macrophages. Autoxidation of NO. leads to nitrosating species which cause deamination of bases. Reaction of NO. with O2.- leads to DNA oxidative damage due to the formation of peroxynitrite which may have HO.-like oxidizing potential. Another possible mechanism of oxidative damage by NO. could be the mobilization of free iron by NO. which could ultimately cause Fenton-type reactions. Therefore, nitric oxide not only leads to deamination of DNA bases but is also an obligatory factor in oxidative damage to DNA.
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PMID:Nitric oxide induces oxidative damage in addition to deamination in macrophage DNA. 757 35


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