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PubMed2001

Peritonitis induces rat cardiac myocytes to promote polymorphonuclear leukocyte emigration and activate endothelial cells: effect of lipopolysaccharide pretreatment.

OBJECTIVE: Peritonitis induced by cecal ligation and perforation results in inflammation and dysfunction of the rat myocardium, an organ remote from the locus of infection. This peritonitis-induced pathology can be prevented by pretreating these animals with lipopolysaccharide before cecal ligation and perforation. In the present study, we assessed a) whether cardiomyocytes obtained from rats subjected to cecal ligation and perforation could induce polymorphonuclear leukocyte transendothelial migration, b) whether these cardiomyocytes could activate endothelial cells (increased proadhesive phenotype), and c) whether these responses could be attenuated by lipopolysaccharide pretreatment. DESIGN: Prospective animal study. SETTING: Experimental animal laboratory. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Lipopolysaccharide pretreated and nonpretreated rats were subjected to cecal ligation and perforation or to laparotomy. Myocytes were isolated 6 hrs after surgery and used for in vitro experiments. MEASUREMENTS AND MAIN RESULTS: Myocytes isolated from cecal ligation and perforation rats promoted migration of polymorphonuclear leukocytes across a rat endothelial cell monolayer, an effect prevented by platelet activating factor receptor antagonists. Myocytes isolated from these animals also increased surface level expression of intercellular adhesion molecule-1 on rat endothelial cells, an effect also prevented by platelet activating factor receptor antagonists. Myocytes isolated from rats pretreated with lipopolysaccharide and then subjected to cecal ligation and perforation did not a) promote polymorphonuclear leukocyte transendothelial migration or b) increase intercellular adhesion molecule-1 surface expression on endothelial cells. CONCLUSIONS: Our findings indicate that induction of peritonitis results in a systemic response that induces cardiac myocytes to become proinflammatory (i.e., these myocytes produce chemotactic factors and activate endothelial cells). This effect of cecal ligation and perforation is abrogated by pretreating animals with lipopolysaccharide before induction of peritonitis.

Animals↗

PubMed2002

Marked difference in pathophysiology between tissue factor- and lipopolysaccharide-induced disseminated intravascular coagulation models in rats.

OBJECTIVE: Tissue factor and lipopolysaccharide frequently have been used to induce disseminated intravascular coagulation in experimental animal models. Although the pathophysiology of disseminated intravascular coagulation may differ according to the agents used to induce it, these previous models have not distinguished between the use of different disseminated intravascular coagulation-inducing agents. In this study, we attempted to evaluate the characteristic features of these agents in two types of disseminated intravascular coagulation models, with special reference to selected hemostatic parameters and pathologic findings in the kidney. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty-seven male Wistar rats, age 6-7 wks, weighing 160-170 g. INTERVENTIONS: Three groups of animals were studied: a control group (n = 8) receiving physiologic saline, a tissue factor-treated group (n = 11) receiving tissue factor 3.75 units/kg, and a lipopolysaccharide-treated group (n = 8) receiving lipopolysaccharide 30 mg/kg; each group sustained infusion for 4 hrs via the tail vein. MEASUREMENTS AND MAIN RESULTS: The degree of hemostatic activation in both types of experimental disseminated intravascular coagulation was identical, based on the results of thrombin-antithrombin III complex levels. Markedly elevated D-dimer concentrations were observed without organ dysfunction or fibrin deposition in the kidney on administration of tissue factor, whereas markedly elevated plasminogen activator inhibitor activity, decreased antithrombin III activity, severe organ failure, and marked fibrin deposition in the kidney were observed for lipopolysaccharide administration. CONCLUSION: Because pathophysiology differed remarkably between the tissue factor- and lipopolysaccharide-induced disseminated intravascular coagulation models in rats, we recommend that they be assessed carefully as distinct entities to determine implications of their experimental and clinical use.

Animals↗

PubMed1999

Influence of FR 167653, an inhibitor of TNF-alpha and IL-1, on the cardiovascular responses to chronic infusion of lipopolysaccharide in conscious rats.

Conscious, male Long Evans rats (350-450 g) chronically instrumented for the measurement of regional haemodynamics, were infused with FR 167653, a dual inhibitor of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) synthesis (0.32 mg/kg/h) for 24 h, beginning 1 h before coinfusion of saline, or with saline for 24 h beginning 1 h before coinfusion of lipopolysaccharide (150 microg/kg/h), or with FR 167653 beginning 1 h before coinfusion of lipopolysaccharide. Animals infused with FR 167653 and saline showed progressive hindquarters vasoconstriction over the 24-h period, but this was not different from the change seen in animals (n = 3) infused with saline alone. However, plasma analysis at the end of the coinfusion of FR 167653 and saline showed substantial elevation in levels of creatine kinase, lactate dehydrogenase, and potassium, consistent with some tissue damage (heart, liver, or skeletal muscle, or a combination of these). Animals coinfused with saline and lipopolysaccharide showed biphasic decreases in mean arterial blood pressure accompanied by renal hyperaemic vasodilatation, and decreases followed by increases in mesenteric and hindquarters flows and vascular conductances. At the end of the infusion period, plasma analysis showed signs of renal dysfunction (elevated creatinine) and hepatic dysfunction (elevated alkaline phosphatase, gamma-glutamyl transferase, and alanine aminotransferase). In the presence of FR 167653, the hypotensive effects of lipopolysaccharide were abolished, but regional haemodynamics were unchanged, as were signs of organ dysfunction. One explanation of these observations is that FR 167653 causes a relative improvement in cardiac function during infusion of lipopolysaccharide, and this opposes the hypotensive effects of the latter, in spite of its persistent vasodilator effects.

Animals↗

PubMed2005

Interleukin-10 blunts the human inflammatory response to lipopolysaccharide without affecting the cardiovascular response.

OBJECTIVE: The objective of this study was to assess the efficacy of variations in dose and timing of administration of recombinant human IL-10 (rhIL-10) on inflammatory and cardiovascular responses in a human endotoxemia model of sepsis. DESIGN: The authors conducted a randomized, placebo-controlled, double-blind trial. SETTING: The study was conducted in a procedure room of an intensive-care unit. PARTICIPANTS: The study comprised 24 healthy male volunteers. INTERVENTIONS: Interventions consisted of intravenous administration of rhIL-10 at 1, 10, or 25 microg/kg either 2 mins or 2 hrs before Escherichia coli lipopolysaccharide (4 ng/kg) or placebo. MEASUREMENTS AND RESULTS: The placebo group receiving lipopolysaccharide alone demonstrated significant, time-dependent changes in vital signs, white blood cell counts, inflammatory cytokine/cortisol levels, and hemodynamic/cardiovascular (including echocardiographic) parameters over the duration of the study. rhIL-10, administered immediately before (concurrent) lipopolysaccharide resulted in decreased temperature and heart rate responses as well as decreased serum levels of proinflammatory cytokines (tumor necrosis factor-alpha, IL-6), IL-1 receptor antagonist, cortisol, and total leukocytes/neutrophils compared with lipopolysaccharide alone. Dose-dependent effects were absent. In contrast, rhIL-10 administration 2 hrs before endotoxin augmented the endotoxin-induced IL-beta and IL-1 receptor antagonist response. rhIL-10 failed to modulate major cardiovascular responses (cardiac output, stroke volume index, ejection fraction, peak systolic pressure/end-systolic volume ratio) to endotoxin in both study groups as assessed by echocardiography. CONCLUSION: Concurrent administration of rhIL-10 suppresses the human inflammatory/stress response but has no effect on the hemodynamic/cardiovascular response to endotoxin. Early administration of rhIL-10 can potentially augment elements of the cytokine inflammatory response to lipopolysaccharide. These findings suggest significant limitations of rhIL-10 as a potential immunomodulatory therapy for sepsis.

Adolescent↗

PubMed2003

Lipopolysaccharide activates nuclear factor-kappaB through toll-like receptors and related molecules in cultured biliary epithelial cells.

To clarify the innate immunity of the intrahepatic biliary tree, we examined expression of Toll-like receptors and intracellular signalings in biliary epithelial cells in response to bacterial components by using cultured biliary epithelial cells (murine biliary cells and human cholangiocarcinoma cell lines). The expression of Toll-like receptors in cultured cells was examined by reverse transcription and PCR and immunohistochemistry. Intracellular signalings after Toll-like receptors activation by lipopolysaccharide was examined by analysis of nuclear factor (NF)-kappaB activation and inhibition studies using inhibitors for NF-kappaB and mitogen-activated protein kinase and blocking antibody. The mRNAs of Toll-like receptors 2, 3, 4, and 5, and related molecules (MD-2, MyD88, and CD14) were detected, and their proteins were expressed in cultured cells. Lipopolysaccharide was shown to bind to the cell surface of cultured cells. Lipopolysaccharide treatment induced the production of TNF-alpha, and nuclear translocation of NF-kappaB and increased NF-kappaB-DNA binding in cultured cells. This induction of TNF-alpha was partially inhibited by anti-Toll-like receptor 4 antibody. The nuclear translocation and increased binding of NF-kappaB by lipopolysaccharide were blocked by addition of MG132, an inhibitor of NF-kappaB. In conclusion, lipopolysaccharide appears to form a receptor complex of CD14, Toll-like receptor 4, MD-2, and MyD88 in cultured biliary epithelial cells and seems to regulate activation of NF-kappaB and synthesis of TNF-alpha. The recognition of pathogen-associated molecular patterns using Toll-like receptors and related molecules in biliary epithelial cells, which is demonstrated in this in vitro study, may participate in an immunopathology of the intrahepatic biliary tree in vivo.

Adult↗

PubMed2006

Role of interleukin-6 in fibrinolytic changes induced by lipopolysaccharide in mice.

We have recently demonstrated that interleukin (IL)-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least partly, via the inhibition of proinflammatory cytokines and chemokines using IL-6-null [IL-6(-/-)] mice and corresponding wild-type mice. Its role in fibrinolytic systems remains undefined, however. The present study elucidated the role of IL-6 in the activity of alpha(2)-plasmin inhibitor, an inhibitor of fibrinolysis, during inflammation induced by intraperitoneal administration of lipopolysaccharide in IL-6(-/-) and wild-type mice. Both IL-6(-/-) and wild-type mice were injected with vehicle or lipopolysaccharide (1 mg/kg). Seventy-two hours later, blood samples were collected and alpha(2)-plasmin inhibitor activity was examined. Lipopolysaccharide challenge induced significant enhancement of alpha(2)-plasmin inhibitor activity as compared with vehicle challenge in wild-type mice, but not in IL-6(-/-) mice. In the presence of lipopolysaccharide, the activity was significantly lower in IL-6(-/-) mice than that in wild-type mice. These results indicate that IL-6 can, at least partly, inhibit the lipopolysaccharide-enhanced fibrinolysis via the enhanced alpha2-plasmin inhibitor activity.

Animals↗

PubMed1998

Formation of superoxide anion in the hepatic sinusoid after lipopolysaccharide challenge.

Using the cytochrome c method, superoxide anion that is released into the hepatic sinusoid was measured after a lipopolysaccharide challenge in a liver perfusion system. Moreover, damages of epithelial cells of the hepatic sinusoid were estimated with scanning electron microscopic analysis and levels of purine nucleoside phosphorylase/GPT ratio. Lipopolysaccharide administration increased the conversion of oxidized cytochrome c into reduced cytochrome c in the perfusate, indicating that superoxide anion was formed in the hepatic sinusoid. This change was associated with increase in levels of portal tumor necrosis factor-alpha and attenuated by the simultaneous administration of superoxide dismutase. Scanning electron microscope analysis revealed that diameters of sinusoidal fenestrae increased in rats treated with lipopolysaccharide, compared with controls. Moreover, levels of purine nucleoside phosphorylase/GPT ratio was significantly increased in the liver perfusate in lipopolysaccharide-treated rats, compared with controls. Superoxide anion in hepatic sinusoid may be one of the pathogenic factors behind damages of epithelial cells of the hepatic sinusoid caused by lipopolysaccharide.

Animals↗

PubMed1991

Ionizing groups in lipopolysaccharides of Pseudomonas cepacia in relation to antibiotic resistance.

Contrary to previous reports, lipopolysaccharides from Pseudomonas cepacia contain a 3-deoxyoct-2-ulosonic acid (probably a single residue). The lipopolysaccharides contain only two phosphate residues, one of which apparently forms a phosphodiester bridge between 4-amino-4-deoxyarabinose and a glucosamine residue in lipid A. The second, unlocated phosphate residue occurs mainly as a monoester in some lipopolysaccharides, and mainly as a diester in others. All lipopolysaccharides lack pyrophosphate residues. The results support the view that the resistance of P. cepacia to cationic antibiotics stems from ineffective binding to the outer membrane, as a consequence of the low number of phosphate and carboxylate groups in the lipopolysaccharide, and the presence of the protonated aminodeoxypentose.

Amino Sugars↗

PubMed1996

Inhibition of nuclear factor kappa B subunit p65 mRNA accumulation in lipopolysaccharide-stimulated human monocytic cells treated with sodium salicylate.

Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of inflammatory mediators such as tumor necrosis factor and interleukin-1. The nature of the nuclear factors involved in regulation of these cytokine genes is still unknown. Nuclear factor kappa B (NF-kappa B; heterodimer of p50 and p65) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with lipopolysaccharide. Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation, and a new mechanism of drug action was suggested recently. Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of NF-kappa B activation by preventing the degradation of NF-kappa B inhibitor "I kappa B", blocking the translocation of NF-kappa B into the nuclear compartment. However, the nature of the subunit involved in this mechanism has not been defined. To examine the mechanisms by which salicylates affect cytokine gene transcription, the amount of active and inactive NF-kappa B and NF-kappa B mRNA, in Porphyromonas gingivalis lipopolysaccharide-stimulated human monocytic cells was assessed. High doses of sodium salicylate suppressed NF-kappa B p65 mRNA accumulation, resulting in suppression of total NF-kappa B, p50 on tissue oligonucleotide had no effects on lipopolysaccharide-induced NF-kappa B activation. The data demonstrate that the p65 subunit of NF-kappa B is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of inflammatory mediators.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

Binding of Actinobacillus actinomycetemcomitans lipopolysaccharides to Peptostreptococcus micros stimulates tumor necrosis factor alpha production by macrophage-like cells.

Peptostreptococcus micros is a gram-positive bacterium that has been associated with periodontitis and endodontic infections. In this study, we hypothesized that P. micros binds the immunomodulating component lipopolysaccharide derived from gram-negative bacteria to increase its capacity to stimulate cytokine production by host cells. The ability of P. micros to bind Actinobacillus actinomycetemcomitans lipopolysaccharide was demonstrated by an enzyme-linked immunosorbent assay and by immunoelectron microscopy. Pretreatment of P. micros cells with A. actinomycetemcomitans lipopolysaccharide was associated with a 49-fold increase in tumor necrosis factor alpha production by human monocytic cells U937 differentiated into adherent macrophages, compared to the stimulation with untreated P. micros. This effect was suppressed by incorporating polymyxin B, a lipid A-binding substance, during treatment of macrophage-like cells with lipopolysaccharide-coated P. micros cells. This is the first study reporting a binding interaction between lipopolysaccharide and a gram-positive bacterium. This interaction represents a new mechanism that could promote the inflammatory response during periodontitis.

Aggregatibacter actinomycetemcomitans↗

PubMed1975

The isolation of two different lipopolysaccharide fractions from various Proteus mirabilis strains.

Four distinct Proteus mirabilis strains were extracted by the phenol/water procedure. After ultracentrifugation of the dialyzed water phase, the pelleted lipopolysaccharide was purified and analyzed. The sugar composition of this lipopolysaccharide fraction I was similar for all four strains, containing only small amounts of strain-specific constituents. A second lipopolysaccharide fraction was isolated from the supernatant above (termed L1 fraction) after removal of nucleic acids. DEAE-cellulose chromatography indicated that this material is not a polysaccharide but rather a water-soluble lipopolysaccharide containing strain-specific constituents such as uronic acids, amino acids, amino sugars, neutral sugars, ethanolamine and phosphate, depending on the strain from which lipopolysaccharide II was isolated.

Amino Acids↗

PubMed1976

[Study of the lipopolysaccharide from Escherichia coli K12 CR34].

The structure of the lipopolysaccharide from Escherichia coli K12, strain CR34 has been investigated. The lipopolysaccharide contains D-galactose, D-glucose, D-glucosamine, L-glycero D-mannoheptose, 2-keto-3-deoxyoctonate and lipid A. The core region does not contain D-glucosamine but contains galactose, glucose, and heptose in the molar ratios 1:3:6. Methylations were performed on the lipopolysaccharide and on the degraded polysaccharide obtained after acetic acid hydrolysis of the lipopolysaccharide. It was found that galactose is in terminal position partly in the form of galactopyranose, partly in the form of galactofuranose. A part of the heptose was found as unsubstituted heptofuranose. A mole of glucose was 1 leads to 2 linked and another mole of glucose was 1 leads to 6 linked. Periodate oxidation of the lipopolysaccharide followed by borohydride reduction eliminates galactose and only a part of glucose and of heptose. A mole of heptose gave mannose and thus it is unsubstituted in C6 and C7. One mole of glucose and one mole of heptose were not degraded by periodate oxidation.

Escherichia coli↗

PubMed1979

A lipopolysaccharide-binding cell-surface protein from Salmonella minnesota. Isolation, partial characterization and occurrence in different Enterobacteriaceae.

1. Protein extracts obtained from Salmonella minnesota Re mutant cells by treatment with EDTA/NaC1 solution contain a protein which exhibits high affinity to bacterial lipopolysaccharides. The isolation and partial characterization of this lipopolysaccharide-binding protein is described. 2. The protein was purified from EDTA extracts by a two-step procedure consisting of ion-exchange chromatography on CM-Sephadex and preparative polyacrylamide gel electrophoresis at pH 9.5. The yield of the total purification procedure was around 16%. 3. The resulting protein preparation was homogeneous on the basis of disc gel electrophoresis, dodecylsulfate gel electrophoresis, isoelectric focusing in polyacrylamide gel and immunoelectrophoresis. 4. The isoelectric point of the protein was found to be 10.3 at 4 degrees C. Its molecular weight determined by dodecylsulfate gel electrophoresis is 15000. Its amino acid composition is characterized by the absence of histidine and proline, a low content in tyrosine and high amounts of alanine, lysine, aspartic and glutamic acid residues, or their respective amides. 5. The lipopolysaccharide-protein association was shown to be mainly due to ionic interactions of the basic protein with negatively charged groups (probably phosphate and pyrophosphate groups) of the lipid A moiety. 6. Purified lipopolysaccharide-binding protein is immunogenic in rabbits, thus enabling the preparation of specific antiserum. 7. The protein is located at the surface of Salmonella minnesota Re mutant cells as revealed by antiserum absorption with total bacteria. Ferritin-labelling studies further demonstrated that it is evenly spread over the entire cell surface. 8. Comparative antiserum absorption studies using smooth and rough strains of Salmonella minnesota, Salmonella typhimurium, Escherichia coli, Klebsiella and Shigella revealed the presence of lipopolysaccharide-binding protein (or a serologically cross-reacting antigen) in most of the strains tested. From these results the protein can be considered as a common antigen of Enterobacteriaceae.

Amino Acids↗

PubMed1982

Isolation, purification, and chemical analysis of the lipopolysaccharide and lipid A of Acinetobacter calcoaceticus NCTC 10305.

The lipopolysaccharide of Acinetobacter calcoaceticus NCTC 10305 (London) was obtained by a modified phenol/chloroform/light petroleum method from the bacterial cells and from the culture medium in yields of 1.6% and 2.2% respectively (based on the bacterial dry weight). On chemical analysis, both preparations proved to be identical. The lipopolysaccharide obtained from the cells was purified by repeated ultracentrifugation, electrodialysis, and precipitation with sodium chloride. It was free of nucleic acids, proteins, and glycans. In the analytical ultracentrifuge, the triethylamine and sodium salt forms of the lipopolysaccharide showed a s20 value of 8.9 S and 51 S, respectively. The lipopolysaccharide consisted of glucosamine, 3-deoxy-D-manno-octulosonic acid, D-glucose, fatty acids, and phosphate in a molar ratio of 2:1:7:6:4. The fatty acids were predominantly lauric acid, 2-hydroxy, and 3-hydroxylauric acid in a molar ratio of 1:1:2. Only 3-hydroxylauric acid was found in amide linkage. On mild acid hydrolysis of the lipopolysaccharide, 65% lipid A were obtained, to which glucosamine was retained quantitatively. It still contained 50% of the original glucose, while one third (15%) of the liberated glucose was in monomeric form.

Acinetobacter↗

PubMed1982

Evidence for different requirements in physical state for the interaction of lipopolysaccharides with the classical and alternative pathways of complement.

The influence of the state of aggregation of lipopolysaccharides upon their ability to interact with serum complement via either the classical or alternative pathway was studied. The anticomplement properties of two chromatographically distinct fractions of a phenol-extracted lipopolysaccharide isolated from Serratia marcescens were assessed by means of the standard sheep erythrocyte hemolytic assay and an alternative pathway-selective kinetic assay using rabbit erythrocytes. Both the high molecular weight PI fraction and the lower molecular weight PII fraction exerted anti-complement activity as determined in the sheep erythrocyte assay. Conversion of fractions PI and PII to their more soluble triethylamine salt forms resulted in a decrease in sedimentation coefficients and a corresponding loss of anticomplement activity. Further, the anticomplement activity of fractions PI and PII in the sheep erythrocyte assay was inhibited by polymyxin B, indicating a role for the lipid A region. Unlike the PII fraction, only the PI fraction can activate serum complement via the alternative pathway. This activity is not inhibited by polymyxin B, indicating that the response is not lipid A-mediated. Significantly, solubilization of the PI fraction with triethylamine had no effect on its ability to activate the alternative pathway. These studies clearly demonstrate that the interaction between lipopolysaccharides and serum complement is influenced by the state of lipopolysaccharide aggregation. However, this appears to be the case for lipopolysaccharide activation of the classical pathway but not of the alternative pathway.

Adult↗

PubMed1983

Effect of reduced membrane lipid fluidity on the biosynthesis of lipopolysaccharide of Escherichia coli.

A low molecular weight precursor of lipopolysaccharide was accumulated under conditions in which the membrane lipids of a fatty acid auxotroph of Escherichia coli were reduced to a non-fluid state. The lipopolysaccharide precursor was detected, by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and autoradiography, in membranes isolated from cells which were pulse-labeled with N-acetyl-[1-14C]glucosamine. The precursor could be chased into mature lipopolysaccharide by returning the membrane lipids to a normal fluid state. Conversion of the precursor to lipopolysaccharide was inhibited by the presence of potassium cyanide or sodium arsenate. The processing of several outer membrane protein precursors, including the promatrix proteins, was also inhibited under these conditions. Preliminary characterization of the lipopolysaccharide precursor was undertaken.

Bacterial Proteins↗

PubMed2006

Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency.

BACKGROUND AND AIMS: Intestinal endotoxin (lipopolysaccharide) is thought to contribute to liver injury in both alcoholic and nonalcoholic steatohepatitis (NASH). Tumor necrosis factor alpha (TNFalpha) is an important mediator of this process and is considered central to the inflammatory response in NASH. This study aimed to investigate the effects of lipopolysaccharide on liver injury in the methionine choline deficient (MCD) nutritional model of NASH, and to determine if TNFalpha is required for the development of steatohepatitis in this model. METHOD: Male C57/BL6 mice received a MCD diet for 4 weeks, whilst a control group received an identical diet supplemented with 0.2% choline bitartrate and 0.3% methionine. At 4 weeks, mice received either an intraperitoneal injection of lipopolysaccharide (0.5 microg/g body mass) or sterile saline, and were killed 24 h thereafter. In a separate study, TNFalpha knockout and wild type C57BL/6 mice received either MCD or control diets for 4 weeks. Serum transaminase levels, liver histology (steatosis, inflammation and apoptosis), hepatic triglyceride concentration and hepatic lipid peroxidation products (conjugated dienes, lipid hydroperoxides and thiobarbituric reactive substances, free and total) were evaluated. RESULTS: Intraperitoneal administration of lipopolysaccharide augmented serum alanine aminotransferase (ALT) levels (P<0.02), hepatic inflammation (P<0.025), apoptosis (P<0.01) and free thiobarbituric acid reactive substances (P<0.025) in MCD mice. TNFalpha knockout mice fed the MCD diet developed steatohepatitis with histological and biochemical changes similar to those seen in wild type counterparts. CONCLUSIONS: Lipopolysaccharide augments liver injury in MCD mice, and TNFalpha is not required for the development of steatohepatitis in MCD mice.

Alanine Transaminase↗

PubMed1995

Strong adjuvant action of Klebsiella O3 lipopolysaccharide and its inhibition of systemic anaphylaxis.

Immunization with lipopolysaccharide from Klebsiella O3 as an immunological adjuvant did not cause the death of mice in systemic anaphylaxis to bovine serum albumin. On the other hand, most mice immunized with lipopolysaccharide from Escherichia coli O111, Klebsiella O4 and Salmonella minnesota did die. Klebsiella O3 lipopolysaccharide enhanced IgM and IgG antibody response to BSA more markedly than Escherichia coli O111 lipopolysaccharide, while it affected the production of IgE antibody only slightly. therefore, it is suggested that the inhibition of systemic anaphylaxis by Klebsiella O3 lipopolysaccharide adjuvant might be related to its strong adjuvant action on IgM and IgG class antibody production, and that high levels of circulating IgM and IgG antibodies might act as blocking antibodies in the development of IgE-mediated systemic anaphylaxis.

Adjuvants, Immunologic↗