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 aim of the present study was to investigate the role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in lipopolysaccharide (LPS)-induced septic rats. Male specific pyrogen-free Wistar rats were deprived food for 24 h before the experiment. Intravenous LPS (3 mg/kg dissolved in sterilized saline) was given to rats 12 h after food removal. Control rats received sterilized saline only. Under diethylether-anesthesia, the pylorus and esophageal sphincters of rats were ligated. Vagotomy also was performed. The stomachs were then irrigated for 3 h with physiological acid solutions containing 0-150 mM HCl plus adequate amount of NaCl. Increases in various ulcerogenic parameters, such as gastric acid back-diffusion, mucosal histamine concentration, luminal hemoglobin (Hb) content and stomach ulcer, were dependent on the concentration of acid solutions irrigated in stomachs of those LPS rats. Gastric vascular permeability also was increased in an acid concentration-related manner. In those LPS rats, high correlation was found between extents of acid back-diffusion and mucosal ulceration. Increased vascular permeability also closely related to the luminal Hb content. Moreover, these ulcerogenic parameters were dose-dependently ameliorated by intraperitoneal ketotifen and ranitidine. Diamine oxidase also was effective in inhibition, but exogenous histamine on the contrary, produced exacerbation of these ulcerogenic parameters. In conclusion, histamine plays a pivotal role in modulating gastric acid back-diffusion and vascular permeability that are greatly associated with hemorrhagic ulcer in septic rats.
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PMID:Role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in septic rats. 1190 49

Actinobacillus pleuropneumoniae is an important pathogen of swine. Lipopolysaccharide (LPS) has been identified as the major adhesin of A. pleuropneumoniae and it is involved in adherence to porcine respiratory tract cells. We previously generated seven rough LPS mutants of A. pleuropneumoniae serotype 1 by using a mini-Tn10 transposon mutagenesis system [Rioux S, Galarneau C, Harel J et al. Isolation and characterization of mini-Tn10 lipopolysaccharide mutants of Actinobacillus pleuropneumoniae serotype 1. Can J Microbiol 1999; 45: 1017-1026]. The purpose of the present study was to characterize these mutants in order to learn more about LPS O-antigen biosynthesis genes and their organization in A. pleuropneumoniae, and to determine the surface properties and virulence in pigs of these isogenic mutants. By mini-Tn10 insertions in rough mutants, four putative genes (ORF12, ORF16, ORF17, and ORF18) involved in O-antigen biosynthesis in A. pleuropneumoniae serotype 1 were found within a region of 18 ORFs. This region is homologous to the gene cluster of serotype-specific O-polysaccharide biosynthesis from A. actinomycetemcomitans strain Y4 (serotype b). Two mutants showed homology to a protein with identity to glycosyltransferases (ORF12); two others had the mini-Tn10 insertion localized in genes encoding for two distinct proteins with identity to rhamnosyltransferases (ORF16 and ORF17) and three showed homology to a protein which is known to initiate polysaccharide synthesis (ORF18). These four ORFs were also present in A. pleuropneumoniae serotypes 9 and 11 that express an O-antigen that serologically cross-reacts with serotype 1. Evaluation of some biological properties of rough mutants seems to indicate that the absence of O-chains does not appear to have an influence on the virulence of the bacteria in pigs and on the overall surface hydrophobicity, charge and hemoglobin-binding activity, or on LAL activation. An acapsular mutant was included in the present study in order to compare the influence of O-chains and capsule polysaccharides on different cell surface properties. Our data suggest that capsular polysaccharides and not O-chains polysaccharides have a major influence on surface properties of A. pleuropneumoniae serotype 1 and its virulence in pigs.
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PMID:Identification of genes involved in biosynthesis of Actinobacillus pleuropneumoniae serotype 1 O-antigen and biological properties of rough mutants. 1198 43

Hemoglobin is an endotoxin (lipopolysaccharide; LPS)-binding protein that synergistically increases the release of proinflammatory cytokines from the innate immune system in response to LPS. It has been suggested that this activity of hemoglobin facilitates the recognition of Gram-negative bacteria in a wound, thereby maximizing immune efficiency. This synergy may be important to the pathogenesis of a broad spectrum of clinical conditions because elevated hemoglobin levels frequently are observed in patients after the transfusion of red cells, trauma, cardiopulmonary bypass surgery, hemolysis, in addition to other disorders. To determine the molecular basis of the specific hemoglobin-LPS synergy, in this article we tested the effects of globin itself on macrophage responses to LPS. Paradoxically, these studies revealed that globin suppressed tumor necrosis factor (TNF) synthesis in LPS-stimulated murine and human macrophage cultures. LPS comigrated with globin on non-denaturing electrophoretic gels, giving direct evidence for binding. Globin specifically inhibited LPS activity in the standard Limulus assay but did not inhibit interleukin-1beta-mediated TNF synthesis. Iron supplementation of macrophage cultures significantly increased interleukin-1beta-induced TNF release. Intraperitoneal administration of globin protected mice against both LPS-induced lethality and experimentally induced bacterial infection. Thus, the heme-iron moiety of hemoglobin, and not the binding of LPS to globin, enhanced macrophage responses to LPS.
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PMID:Globin attenuates the innate immune response to endotoxin. 1206 85

The binding of lipopolysaccharide (LPS, also known as bacterial endotoxin) to human hemoglobin is known to result in oxidation of hemoglobin to methemoglobin and hemichrome. We have investigated the effects of the LPSs from smooth and rough Escherichia coli and Salmonella minnesota on the rate of oxidation of native oxyhemoglobin A0 and hemoglobin cross-linked between the alpha-99 lysines. For cross-linked hemoglobin, both smooth LPSs produced a rate of oxidation faster than the corresponding rough LPSs, indicating the importance of the binding of LPS to the hemoglobin. The effect of the LPS appeared to be largely on the initial fast phase of the oxidation reaction, suggesting modification of the heme pocket of the alpha chains. For hemoglobin A0, the rates of oxidation produced by rough and smooth LPSs were very similar, suggesting the possibility that the effect of the LPSs was to cause dissociation of hemoglobin into dimers. The participation of cupric ion in the oxidation process was demonstrated in most cases. In contrast, the rate of oxidation of cross-linked hemoglobin by the LPSs of both the rough and smooth E. coli was not affected by the presence of chelators, suggesting that cupric ion had previously bound to these LPSs. Overall, these data suggest that the physiological effectiveness of hemoglobin solutions now being developed for clinical use may be decreased by the presence of lipopolysaccharide in the circulation of recipients.
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PMID:The oxidative effect of bacterial lipopolysaccharide on native and cross-linked human hemoglobin as a function of the structure of the lipopolysaccharide. 1223 May 76

CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide (LPS). We also show that LPS induces shedding of CD163 from the surface of isolated monocytes, identifying shedding from monocytes and macrophages as a likely mechanism for the endotoxemia-associated rise in plasma CD163 in vivo. Studies using the inhibitor TAPI-0 indicate that a metalloproteinase is responsible for LPS-mediated shedding of CD163. Finally, we demonstrate a marked increase in surface CD163 expression on circulating monocytes 24 h following experimental endotoxemia. These findings show that CD163 is rapidly mobilized in response to bacterial endotoxin. As hemoglobin can bind LPS and enhance its toxicity, it will be important to determine how cell surface and soluble CD163 influence inflammatory processes during sepsis.
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PMID:Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163. 1237 40

In the present study, we investigated the effect of nitric oxide (NO) and prostaglandins (PGs) on the production of arachidonate and L-arginine metabolites. We found that in the estrogenized rat uterus lipopolysaccharide (LPS) 5mg/kg induced NO and PGs synthesis simultaneously. The uteri were incubated with different doses of an NO donor: NP 300 and 600 microM. The results indicate that both doses of NP produce a significant increase (P<0.01) in all prostanoids evaluated. The stimulatory effect was completely reversed by the addition of 2 microg/ml of hemoglobin (Hb), an NO scavenger. However, NOS inhibitor, N(G)-L-monomethyl arginine had no effect on basal prostanoid production. We also studied NO synthesis in the presence of different PGs concentration. We found that PGF(2alpha) and PGD(2) were capable of reversing LPS stimulation on NO synthesis (P<0.05), in all the doses evaluated. On the other hand, PGE(2) 10(-10) and 10(-9)M potentated LPS effect (P<0.001). These results suggest that in the estrogenized rat uterus, the synthesis of cyclooxygenase metabolites is positively regulated by NO, while NO synthesis regulation depends on the PGs evaluated.
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PMID:Crosstalk between nitric oxide synthase and cyclooxygenase metabolites in the estrogenized rat uterus. 1262 24

We investigated the effects of iron on the production of nitric oxide (NO), inducible NO synthase (iNOS), and plasma cytokines induced by lipopolysaccharide (LPS) in vivo. Male Wistar rats were preloaded with a single intravenous injection of saccharated colloidal iron (Fesin, 70 mg iron/kg body weight) or normal saline as a control, and then given an intraperitoneal injection of LPS (5.0 mg/kg body weight). Rats, preloaded with iron, had evidence of both iron deposition and strong iNOS induction in liver Kupffer cells upon injection of LPS; phagocytic cells in the spleen and lung had similar findings. LPS-induced NO production in iron-preloaded rats was significantly higher than control rats as accessed by NO-hemoglobin levels measured by ESR (electron spin resonance) and NOx (nitrate plus nitrite) levels. Western blot analysis showed that iron preloading significantly enhanced LPS-induced iNOS induction in the liver, but not in the spleen or lung. LPS-induced plasma levels of IL-6, IL-1beta, and TNF-alpha were also significantly higher in iron-preloaded rats as shown by ELISA, but IFN-gamma levels were unchanged. We conclude that colloidal-iron phagocytosed by liver Kupffer cells enhanced LPS-induced NO production in vivo, iNOS induction in the liver, and release of IL-6, IL-1beta, and TNF-alpha.
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PMID:Saccharated colloidal iron enhances lipopolysaccharide-induced nitric oxide production in vivo. 1275 53

The interaction of purified alpha alpha cross-linked hemoglobin (alpha alpha Hb) with a pentaacylated mutant lipopolysaccharide (pLPS) and the corresponding lipid A (pLA) was studied biophysically and the effects correlated with data from biological assays, i.e. cytokine induction (tumor necrosis factor-alpha) in human mononuclear cells and the Limulus amebocyte lysate assay. Fourier transform infrared spectroscopic and Zeta-Sizer experiments indicated an electrostatic as well as a non-electrostatic binding of alpha alpha Hb to the hydrophilic and to the hydrophobic moieties of the endotoxins with an increase of the inclination angle of the pLA backbone, with respect to the membrane surface, from 25 degrees to more than 50 degrees. Small angle synchrotron radiation x-ray diffraction measurements indicated a reorientation of the lipid A aggregates from a multilamellar into a cubic structure as a result of alpha alpha Hb interaction. Thus, in the absence of alpha alpha Hb, the molecular shape of the pentaacyl samples was cylindrical with a moderate inclination of the diglucosamine backbone, whereas, in the presence of the protein, the shape was conical, and the inclination angle was high. The cytokine-inducing capability in human mononuclear cells, negligible for the pure pentaacylated compounds, increased markedly in the presence of alpha alpha Hb in a concentration-dependent manner. In the Limulus assay, the pentaacylated samples were active a priori, and their activity was enhanced following binding to alpha alphaHb, at least at the highest protein concentrations. The data can be understood in the light of a reaggregation of the endotoxins because of alpha alpha Hb binding, with the endotoxin backbones then readily accessible for serum and membrane proteins. By using fluorescence resonance energy transfer spectroscopy, an uptake of the endotoxin-Hb complex into phospholipid liposomes was observed, which provides a basis for cell activation.
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PMID:Cross-linked hemoglobin converts endotoxically inactive pentaacyl endotoxins into a physiologically active conformation. 1367 76

Hemoglobin, its chains, and myoglobin enhance the antibiotic activity of colicine K. These proteins also interact with colicine K and other O antigens to alter their serological activity. The hemoglobin proteins did not alter the serological activities of three Pneumococcus polysaccharides or T4 bacteriophage DNA antigens but did alter the antigenic activity of fetuin. Interaction of hemoglobin and colicine K resulted in a retardation of colicine K antibiotic moiety as measured by gel filtration but did not affect the gel filtration properties of the lipopolysaccharide moiety.
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PMID:ENHANCEMENTS OF ANTIBIOTIC ACTIVITY OF COLICINE K AND ALTERATION OF SEROLOGICAL PROPERTIES OF COLICINE K AND ENDOTOXINS. 1426 71

The study is undertaken to determine the effect of adrenal corticosteroid depletion after adrenalectomy on carbohydrate, protein and fat metabolism as well as maturation and functional efficacy of the immunocompetent cells. Beside biochemical and hematological parameters, whether in vivo glucocorticoid depletion has any modulatory effects on splenic macrophage responses to bacterial challenge with regards to intracellular killing, nitric oxide release and cellular integrity, were determined. Major findings of our study indicate that blood glucose, urea and total inorganic phosphate levels showed a time dependent increase in adrenalectomized rats compared to control. Total glycogen content in liver was decreased gradually due to adrenal corticosteroid insufficiency. Hematological parameters like hemoglobin concentration, hematocrit value, total leukocyte count and differential count were also found to increase in the adrenalectomized group with respect to intact group. From the functional study of immunocompetent cells, intracellular killing capacity of splenic macrophages recovered from control and adrenalectomized rats after 10 and 20 days of adrenalectomy showed no significant alteration; however, the function of splenic macrophages recovered from rats after 30 days of adrenalectomy showed altered response. Nitric oxide released from splenic macrophages of adrenalectomized rats was less than that of control animal even after stimulation with lipopolysaccharide. DNA fragmentation assay showed a lesser degree of fragmentation of splenic macrophages obtained from adrenalectomized rats indicating, apoptotic death of cells in this group decreases. Adrenal corticosteroid insufficiency due to adrenalectomy interferes with metabolic and hematopoietic functions and modulates the development and maintenance of normal immunitary status, which in turn influences the inflammatory response.
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PMID:Metabolic and immunological responses associated with in vivo glucocorticoid depletion by adrenalectomy in mature Swiss albino rats. 1455 Aug 55


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