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)

The molecular basis of the immunotoxic effect of ammonium metavanadate on signal transduction involved in macrophage activation was studied in resident peritoneal macrophages (PEM) and a murine macrophage-like cell line, J774. A fourfold elevation in cytosolic free calcium levels was observed within 10 s following lipopolysaccharide (LPS) stimulation of the non-vanadate-exposed controls both in vitro and in vivo; the levels returned to prestimulation values within 70 s. Exposure to phorbol ester (PMA) did not result in any appreciable change in cytosolic free calcium levels. Compared to untreated controls, treatment with vanadate caused a significant elevation in basal cytosolic calcium levels. Such elevation was not enhanced further by LPS. LPS stimulation of macrophages also resulted in a significant elevation of membrane-associated protein kinase C (PKC) activity, which was, however, inhibited in a dose-dependent manner by vanadate in both in vitro and in vivo studies. Exposure to PMA also resulted in a significant elevation of membrane-associated PKC activity; vanadate treatment at lower levels did not cause downregulation, indicating that vanadate at these levels interfered with the receptor-mediated events rather than the enzyme directly. Vanadate at higher exposure levels inhibited the activity even in PMA-stimulated macrophages. No significant difference occurred in cytosolic PKC activities in control macrophages; vanadate treatment at lower levels resulted in a significant elevation of cytosolic PKC activities following stimulation with LPS or PMA, indicating that vanadate might be interfering with the translocation process.
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PMID:Modulation of macrophage activation by ammonium metavanadate. 897 29

In rats injected with bacterial lipopolysaccharide (LPS; 5 gamma mg/g body weight [BWT]), the toxin provokes death within 24 h in 23% of the animals and, in surviving rats, causes a decrease in BWT, hyperlactacidemia, hyperlipacidemia, and hyperketonemia, as well as depletion of both liver and muscle glycogen content. In the liver, LPS severely lowers the ATP and total adenine nucleotide content, ATP/ADP ratio, and adenylate charge. In hepatocytes from LPS-injected rats, the oxidation of D-glucose is first increased 2 h after administration of the toxin, despite close-to-normal phosphorylation of the hexose. In hepatocytes prepared from rats killed 24 h after injection of LPS, the phosphorylation of D-glucose, its incorporation into glycogen, and its oxidation are all severely impaired. This sequence of changes, which coincides with a decreased ratio between pyruvate and lactate production from exogenous D-glucose, is comparable to that found with agents that uncouple oxidative phosphorylation. The injection of LPS also alters the metabolic response of hepatocytes to the dimethyl ester of succinic acid (SAD), in terms, for instance, of the sparing action of the ester upon both the production of 14CO2 by hepatocytes prelabeled with L-[U-14C] glutamine and the output of NH4+, and its inhibitory action on glycogenolysis and futile cycling in the reactions catalyzed by glucokinase and glucose-6-phosphatase. Nevertheless, the infusion of SAD protects the rats against the deleterious effect of LPS upon such variables as the plasma concentration of free fatty acids and beta-hydroxybutyrate, the liver ATP content, and the oxidation of D-glucose, as well as the pyruvate/lactate ratio, in hepatocytes prepared from the LPS-injected rats. The infusion of SAD also virtually suppresses lethality in the LPS-injected animals. It is proposed, therefore, that the infusion of succinic acid esters may represent a novel therapeutic approach in endotoxemia and multiple-organ failure.
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PMID:Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia. 917 84

Hosts exposed to vanadium (V) display a subsequent decrease in their resistance to infectious microorganisms. Our earlier studies with rats inhaling occupationally relevant levels of V (as, ammonium metavanadate, NH4VO3) indicated that several nascent/inducible functions of pulmonary macrophages (PAM) were reduced. In the present study, V-exposed rats were examined to determine whether some of the same effects might also occur in situ. Rats were exposed nose-only to air or 2 mg V/m3 (as NH4VO3) for 8 h/d for 4 d, followed, 24 h later, by intratracheal (it) instillation of polyinosinic:polycytidilic acid (polyl:C) or saline. Analysis of lavaged lung cells/fluids after polyl:C instillation indicated that total lavageable cell/neutrophil numbers and protein levels, while significantly elevated in both exposure groups (as well as in saline-treated V-exposed rats), were always greater in V-exposed hosts. Exposure to V also affected the inducible production of interleukin 6 (IL-6) and interferon gamma (IFN gamma), but apparently not that of tumor necrosis factor-alpha (TNF alpha) or IL-1. Although polyl:C induced significant increases in lavage fluid IL-6 and IFN gamma levels in both exposure groups, levels were greater in V-exposed rats. If calculated with respect to total lavaged protein, however, V-exposed rats produced significantly less cytokine. Following polyl:C instillation, there were no marked exposure-related differences in basal or stimulated superoxide anion production by pooled lavaged cells or PAM specifically. With V-exposed rats, pooled cells recovered 24 h after saline instillation displayed reduced production (in both cases) compared to the air control cells; PAM-specific production was affected only after stimulation. In both exposure groups, polyl:C caused decreased superoxide production in recovered cells. Though less apparent with pooled cells, there was a time post polyl:C instillation-dependent decrease in stimulated PAM-specific superoxide production; this effect was greater in PAM from V-exposed rats than in PAM from air controls. Phagocytic activity of PAM from rats in both exposure groups was significantly increased by polyl:C instillation, although total activity in cells obtained from V-exposed rats was always significantly lower compared to air control cells. Our results indicate that short-term, repeated inhalation of occupationally relevant levels of V by rats modulates pulmonary immunocompetence. Modified cytokine production and PAM functionality in response to biological response modifiers (such as lipopolysaccharide, IFN gamma, or polyl:C) may be, at least in part, responsible for the increases in bronchopulmonary disease in humans occupationally exposed to V.
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PMID:Effects of vanadium upon polyl:C-induced responses in rat lung and alveolar macrophages. 924 30

Capsular antigen (C-antigen) was isolated from culture fluid of V. cholerae serovar 0139 strain P16064 4-fold fractionation by (NH4)2SO4 after Weinblatt (1980). Electrophoretic separation in PAAG-SDS revealed two protein subunits with molecular weights 38 +/- 2 and 61 +/- 2 KD in the C-antigen and whole-cell lysates of two strains (MO45 and P16064) of V. cholerae serovar 0139. Murine polyclonal anticapsular antibodies reacted with these protein subunits in immunoblotting, as well as with two rapidly migrating carbohydrate components. After proteinase treatment of the C-antigen and cell lysates from opaque colonies these antibodies helped detect two high-molecular zones in addition to rapidly migrating ones. C-antigen protects from death 75% of mice infected with V. cholerae 0.139 and 43% (P < 0.05) of those infected with V. cholerae eltor 230. The protective properties of C-antigen are due to lipopolysaccharide (LPS) but not to the protein component. The immunogenicity of LPS contained in the C-antigen is selective, whereas LPS isolated from biomass of V. cholerae 0139 cells possesses similar protective activity towards the homologous strain (49.5%) and the agent of Eltor cholera (50.0%).
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PMID:[Some immunochemical and immunobiological properties of Vibrio cholerae serovar 0139 capsule antigen]. 929 5

Our previous studies have shown that the degree of damage to a liposome corresponds to the variability of the animal species from which the serum comes, and that a complement activating factor (CAF) plays an important role in inducing the activation of the complement system, ultimately leading to the lysis of the liposomes. In this study, our attention focused on the characterization of the bovine serum factor (bCAF) that is involved in complement-mediated immune lysis of the liposome. The active fraction containing CAF partially purified with PEG and ammonium sulfate results in marked activation of the complement system via the alternative pathway when interacted with CAF-depleted serum, whereas the active fraction or CAF-depleted serum alone does not activate the complement. The interaction between lipopolysaccharide (LPS), heparin, zymosan or their mixture in place of CAF and CAF-depleted serum does not result in any significant activation of the complement system. Results from pretreatment with rabbit anti-bovine IgM IgG and rabbit anti-bovine IgG IgG indicate that activation of the complement system is not attributable to the antibody which is generally involved in activation of complement via the classical pathway. The results have further been proven by pretreatment with Concanavalin A (Con A) sepharose and protein G sepharose ruling out the possibility of antibody-mediated activation of complement. Our studies on collagenase and trypsin digestion demonstrate that the relative activity of CAF does not diminish with increase in collagenase concentration, and decreases with increase in trypsin concentration, strongly indicating that CAF does not have a collagen-like domain in its structure. The relative activity of CAF is dramatically inhibited after reduction with 2-mercaptoethanol (2-ME), clearly demonstrating that CAF is sensitive to reduction with 2-ME and confirming a sulhydryl-dependent protein. The optimal activity of CAF is observed in the range of 35-45 degrees C and its half-life at 37 degrees C is about 105 h. Furthermore, the relative activity of CAF increases and gradually approaches a plateau level with the increase of Mg2+ concentration. Obviously, complement activation induced by CAF depends on adequate Mg2+ concentration, confirming that this dependence is characteristic of the alternative pathway.
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PMID:Characterization of bovine serum factor triggering the lysis of liposomes via complement activation. 958 79

The protective effects of 5,6,7,8-tetrahydroneopterin (NH4) against radiation injury in mice were studied. (C57BL/6xA/J)F1 (B6A) mice received a single whole-body irradiation dose of 200, 400, 700 or 800 cGy of X-rays. NH4 (30 mg/kg body weight) or phosphate-buffered saline (PBS) was injected intraperitoneally into irradiated mice 10 min before and after the irradiation and again after 6 h. All mice which received the 800 cGy radiation+PBS died between 8 and 11 days after the treatment. In contrast, those which also received NH4 demonstrated a significantly prolonged survival time and 40% lived more than 5 months. Total numbers of thymocytes and spleen cells on day 5 post-irradiation were dramatically reduced in line with the radiation dose. The survival was significantly enhanced by NH4 in treated mice. The proliferation of spleen cells in mice stimulated by concanavalin A (Con A) or lipopolysaccharide (LPS) was also greater in NH4 treated mice. The immune response of survivors 5 months after 800 cGy+NH4 treatments, against Con A, LPS, allogenic mouse, and sheep red blood cells had essentially recovered to the levels of normal mice. These results indicate that NH4 had an important role in modifying radiation injury.
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PMID:Protective effects of 5,6,7,8-tetrahydroneopterin against X-ray radiation injury in mice. 1010 Dec 56

The standard enzyme-linked immunosorbent assay (ELISA) for anticardiolipin antibodies (ACA) detects a heterogenous group of antibodies against cardiolipin on its own, beta2-glycoprotein I (beta2GPI), and, potentially, other phospholipid-binding plasma proteins from bovine or human origin. In an attempt to identify new proteic targets of ACA, we selected 6 patients who possessed cofactor-dependent ACA but no antibody to human or bovine beta2GPI detectable in the beta2GPI-ELISA. Three of these samples proved to recognize beta2GPI in combination with cardiolipin, but not beta2GPI directly immobilized on gamma-irradiated polystyrene or agarose beads. In the other cases, the component required for ACA binding was purified from adult bovine serum or plasma by means of ammonium sulfate precipitation and chromatography on Phenyl-Sepharose, diethyl aminoethyl (DEAE)-cellulose, heparin-Ultrogel, and Sephacryl S-300 columns. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis coupled to N-terminal amino acid microsequencing identified the cofactors of patients no. 4, 5, and 6 ACA as lipopolysaccharide binding protein (LBP), complement C4b-binding protein (C4BP), and the thrombin-antithrombin (AT) complex, respectively. Adsorption of each of these cofactor preparations with cardiolipin liposomes led to suppression of ACA reactivity, concomitant with the loss of bands from SDS gels corresponding to sequenced material. Bacterial lipopolysaccharide (which forms high-affinity complexes with LBP) specifically neutralized the cofactor activity of the LBP preparation in a concentration-dependent manner. Bovine serum and plasma, as well as the C4BP preparation, optimally supported the binding of a rabbit anti-C4BP antiserum to immobilized cardiolipin. The binding of a rabbit anti-AT antiserum to solid-phase cardiolipin was sustained by the thrombin-AT preparation and bovine serum, but neither by bovine plasma nor by native AT, thus reproducing the behavior of patient no. 6 ACA. Taking advantage of the restricted recognition by the latter ACA of a cofactor from bovine origin appearing upon clotting, we studied the generation of such activity in human plasma supplemented with bovine AT or bovine prothrombin before clotting. In these conditions, patient no. 6 antibody binding to cardiolipin required the addition of bovine AT, whereas addition of bovine prothrombin alone was ineffective. We therefore concluded that those ACA targeted bovine AT once it has been modified/cleaved by thrombin. These findings underline the wide heterogeneity of ACA and the links that may exist between various coagulation pathways, inflammation and the complement system.
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PMID:Some anticardiolipin antibodies recognize a combination of phospholipids with thrombin-modified antithrombin, complement C4b-binding protein, and lipopolysaccharide binding protein. 1036 Nov 22

Our aim was to examine whether lipopolysaccharide of Escherichia coli, polyamines of dietetic and/or bacterial origin, and products of the bacterial metabolism influence cell proliferation in epithelial cells from the colon and small intestine. Lipopolysaccharide of Escherichia coli 0111:B4 was incubated with cultures from human colonic mucosa. The mitoses were arrested with Vincristine and the total number of metaphases per crypt was counted. In addition, lipopolysaccharide was incubated with a human colonic epithelial cell line from adenocarcinoma (LS-123 cells) and with a nontransformed small intestinal cell line from germ-free rats (IEC-6 cells) for 24 h. In the last 4 h, the cells were labeled with tritiated thymidine. The cells were incubated with putrescine, cadaverine, and spermidine at 10(-11)-10(-3) M and with acetic acid (10(-5)-10(-1) M), acetaldehyde (10(-10)-10(-4) M) and ammonium chloride (1-20 mM). Lipopolysaccharide of Escherichia coli increased the number of arrested metaphases in human colonic crypts and DNA synthesis in L-123 and IEC-6 cells (P < 0.001). All polyamines increased DNA synthesis in the colonic and small intestinal cell lines, the effects being more marked for putrescine (P < 0.001). The higher concentrations of acetic acid increased DNA synthesis in both epithelial cell lines (P < 0.001). Acetaldehyde slightly decreased DNA synthesis in LS-123 cells at cytotoxic concentrations. Ammonium chloride did not significantly affect DNA synthesis. The final concentration of nonionized ammonia was less than 3%. It is concluded that lipopolysaccharides of Escherichia coli and intraluminal factors derived from microorganisms increase cell proliferation in human colonic crypts and intestinal epithelial cell lines.
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PMID:Lipopolysaccharide of Escherichia coli, polyamines, and acetic acid stimulate cell proliferation in intestinal epithelial cells. 1047 54

A Citrobacter sp. accumulated uranyl ion (UO2(2+)) via precipitation with phosphate ligand liberated by phosphatase activity. The onset and rate of uranyl phosphate deposition were promoted by NH4(+), forming NH(4)UO(2)PO(4), which has a lower solubility product than NaUO(2)PO(4). This acceleration decoupled the rate-limiting chemical crystallization process from the biochemical phosphate ligand generation. This provided a novel approach to monitor the cell-surface-associated changes using atomic-force microscopy in conjunction with transmission electron microscopy and electron-probe X-ray microanalysis, to visualize deposition of uranyl phosphate at the cell surface. Analysis of extracted surface materials by (31)P NMR spectroscopy showed phosphorus resonances at chemical shifts of 0.3 and 2.0 p.p.m., consistent with monophosphate groups of the lipid A backbone of the lipopolysaccharide (LPS). Addition of fUO2(2+) to the extract gave a yellow precipitate which contained uranyl phosphate, while addition of Cd(2+) gave a chemical shift of both resonances to a single new resonance at 3 p.p.m. Acid-phosphatase-mediated crystal growth exocellularly was suggested by the presence of acid phosphatase, localized by immunogold labelling, on the outer membrane and on material exuded from the cells. Metal deposition is proposed to occur via an initial nucleation with phosphate groups localized within the LPS, shown by other workers to be produced exocellularly in association with phosphatase. The crystals are further consolidated with additional, enzymically generated phosphate in close juxtaposition, giving high loads of LPS-bound uranyl phosphate without loss of activity and distinguishing this from simple biosorption, or periplasmic or cellular metal accumulation mechanisms. Accumulation of 'tethered' metal phosphate within the LPS is suggested to prevent fouling of the cell surface by the accumulated precipitate and localization of phosphatase exocellularly is consistent with its possible functions in homeostatis and metal resistance.
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PMID:Enzymically mediated bioprecipitation of uranium by a Citrobacter sp. : a concerted role for exocellular lipopolysaccharide and associated phosphatase in biomineral formation. 1093 90

Recent observations demonstrated that the antimalarial drug chloroquine (CQ) can kill the opportunistic fungus Cryptococcus neoformans. Since CQ blunts lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha release, it was hypothesized that this drug would also interfere with the inflammatory response to C. neoformans and Candida albicans, another fungal opportunist. CQ inhibited TNF-alpha release from peripheral blood mononuclear cells from healthy and human immunodeficiency virus-positive donors without affecting NF-kappaB activation. CQ reduced TNF-alpha mRNA levels by a pH-dependent mechanism in a manner similar to 2 unrelated alkalizing drugs (ammonium chloride and bafilomycin), which also inhibited TNF-alpha gene expression. Although CQ inhibited release of interleukin (IL)-1beta and IL-6, it did not affect IL-10 or macrophage inflammatory protein-1alpha production. Thus, CQ interferes with fungus-induced TNF-alpha expression by a mechanism that probably depends on the alkalization of endolysosomes. This contrasts with CQ's reported pH-independent inhibition of LPS-stimulated TNF-alpha release and suggests that the mechanism of CQ's anti-inflammatory effects is stimulus specific.
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PMID:Chloroquine antagonizes the proinflammatory cytokine response to opportunistic fungi by alkalizing the fungal phagolysosome. 1123 11


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