SEARCH · PubMed Health

Results for “LIPOPOLYSACCHARIDES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMedDate not supplied

Fowl cholera: protection against Pasteurella multocida by ribosome-lipopolysaccharide vaccine.

Ribosomal protein from Aspergillus fumigatus substituted for intact ribosomes in potentiating the immunogenicity of Pasteurella multocida lipopolysaccharide. Ribosomal protein behaved as a carrier for the lipopolysaccharide. The basic protein methylated albumin, but not protamine sulfate, substituted for ribosomal protein as a carrier for lipopolysaccharide. Synthetic single- and double-stranded polynucleotides did not function as an adjuvant to potentiate the immunogenicity of lipopolysaccharide or methylated albumin-lipopolysaccharide complexes. Double-stranded polynucleotide (poly A:poly U), added as an adjuvant for methylated albumin-lipopolysaccharide vaccine, produced sera with lowered passive hemagglutination antibodies to lipopolysaccharide, but it did not influence protection against challenge with P. multocida. No differences in protection were observed between different lines of specific-pathogen-free white leghorn chickens given ribosome-lipopolysaccharide vaccine. Humoral protection, demonstrated by passive-protection tests, was induced by ribosome-lipopolysaccharide vaccine. Cell-mediated immunity was not detected by delayed-type hypersensitivity skin test reactions.

Animals↗

PubMed1993

Gram-negative bacterial lipopolysaccharide impairs hyaluronan clearance in vivo and its uptake by the isolated, perfused rat liver.

The purpose of this investigation was to examine the effect of gram-negative bacterial lipopolysaccharide on hyaluronan concentration in blood plasma, hyaluronan removal from the blood and hyaluronan uptake by isolated, perfused rat liver. Intravenous administration of Escherichia coli lipopolysaccharide to rats markedly increased plasma hyaluronan concentration in a dose-dependent manner. One day after lipopolysaccharide challenge (0.1 or 1.0 mg per 100 gm body wt), plasma hyaluronan levels were 570.7 +/- 66.8 ng x ml-1 and 1,951.0 +/- 120.3 ng x ml-1, respectively, as compared with 94.2 +/- 12.2 ng x ml-1 in the time-matched control animals. Removal of intravenously injected hyaluronan (30 micrograms per 100 gm body wt) was suppressed 32% by lipopolysaccharide administration (100 micrograms per 100 gm body wt). At the same dose, lipopolysaccharide induced a severe inhibition (60% to 80%) of hyaluronan uptake by perfused livers isolated 3 or 24 hr after lipopolysaccharide administration. The inhibitory effect of lipopolysaccharide on hyaluronan uptake by the isolated, perfused liver was not abolished by pretreatment with either antibodies to tumor necrosis factor-alpha IgG or indomethacin, an inhibitor of the cyclooxygenase pathway. Continuous intravenous infusion of recombinant murine tumor necrosis factor-alpha for 18 to 20 hr did not affect plasma hyaluronan concentration. These data suggest that neither tumor necrosis factor-alpha, an early cytokine induced by lipopolysaccharide, nor prostaglandins are involved in the mechanism of lipopolysaccharide-induced inhibition of hyaluronan uptake by the perfused rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2002

Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation.

Endogenous gut-derived bacterial lipopolysaccharides have been implicated as important cofactors in the pathogenesis of liver injury. However, the molecular mechanisms by which lipopolysaccharides exert their effect are not entirely clear. Recent studies have pointed to proinflammatory cytokines such as tumor necrosis factor-alpha as mediators of hepatocyte injury. Within the liver, Kupffer cells are major sources of proinflammatory cytokines that are produced in response to lipopolysaccharides. This review will focus on three important molecular components of the pathway by which lipopolysaccharides activate Kupffer cells: CD14, Toll-like receptor 4, and lipopolysaccharide binding protein. Within the liver, lipopolysaccharides bind to lipopolysaccharide binding protein, which then facilitates its transfer to membrane CD14 on the surface of Kupffer cells. Signaling of lipopolysaccharide through CD14 is mediated by the downstream receptor Toll-like receptor 4 and results in activation of Kupffer cells. The role played by these molecules in liver injury will be examined.

Acute-Phase Proteins↗

PubMed2003

Systemic responsiveness to lipopolysaccharide and polymorphisms in the toll-like receptor 4 gene in human beings.

BACKGROUND: The response to lipopolysaccharide exposure is highly variable and might be a result of genetic diversity between individuals. The toll-like receptor 4 (TLR-4) is the principal receptor for lipopolysacharide. OBJECTIVES: We investigated the association between single-nucleotide polymorphisms in the TLR4 locus and levels of systemic inflammatory markers in response to lipopolysaccharide. METHODS: Healthy subjects (n = 116) were genotyped for the most frequent polymorphisms found in the promoter and coding region of the TLR4 gene (-2026A/T, -1607T/C, +896A/G, and +1196C/T relative to the translation start site). Subjects were challenged with 20 microg lipopolysaccharide by inhalation. RESULTS: Polymorphisms at +896 and +1196 were in complete linkage disequilibrium, and no homozygotes for the less common allele, G and T respectively, were found. After lipopolysaccharide inhalation, subjects heterozygous for either TLR-4/+896 or TLR4/+1196 had significantly lower numbers of white blood cell counts and lower levels of C-reactive protein and lipopolysaccharide-binding protein compared with homozygotes with the common allele. None of the heterozygous subjects (n = 18) except 1 were high responders to lipopolysaccharide (defined as a rise in C-reactive protein > 10 mg/L), whereas 36 of 98 homozygous subjects were high responders (P <.02). No association was observed between the TLR-4/-2026 and TLR-4/-1607 polymorphisms and lipopolysaccharide responsiveness. CONCLUSION: The single-nucleotide polymorphisms at position +896 or +1196 in the TLR-4 gene is associated with systemic inflammatory hyporesponsiveness to inhaled lipopolysaccharide.

Acute-Phase Proteins↗

PubMed2005

Crystal structure of CD14 and its implications for lipopolysaccharide signaling.

Lipopolysaccharide, the endotoxin of Gram-negative bacteria, induces extensive immune responses that can lead to fatal septic shock syndrome. The core receptors recognizing lipopolysaccharide are CD14, TLR4, and MD-2. CD14 binds to lipopolysaccharide and presents it to the TLR4/MD-2 complex, which initiates intracellular signaling. In addition to lipopolysaccharide, CD14 is capable of recognizing a few other microbial and cellular products. Here, we present the first crystal structure of CD14 to 2.5 angstroms resolution. A large hydrophobic pocket was found on the NH2-terminal side of the horseshoe-like structure. Previously identified regions involved in lipopolysaccharide binding map to the rim and bottom of the pocket indicating that the pocket is the main component of the lipopolysaccharide-binding site. Mutations that interfere with lipopolysaccharide signaling but not with lipopolysaccharide binding are also clustered in a separate area near the pocket. Ligand diversity of CD14 could be explained by the generous size of the pocket, the considerable flexibility of the rim of the pocket, and the multiplicity of grooves available for ligand binding.

Amino Acid Sequence↗

PubMed1964

LIPOPOLYSACCHARIDE OF THE GRAM-NEGATIVE CELL WALL.

The use of mutants of Salmonella typhimurium in which biosynthesis of specific lipopolysaccharide precursors is blocked has made possible both biosynthetic studies and structural analyses which provide the basis for the structure of the core polysaccharide shown in Fig. 6. The simplest mutant, which is unable to synthesize UDP-glucose, forms only the backbone structure, containing heptose, phosphate, and keto-deoxyoctonate. To this backbone are attached side chains containing glucose, galactose, and N-acetylglucosamine. The resulting core structure is found in the lipopolysaccharide of the rough strain, as well as in that of the GDP-mannose- deficient mutant. In the wild type organism, long O-antigenic chains composed of repeating units containing galactose, mannose, rhamnose, and abequose are linked to the core, perhaps to the N-acetylglucosamine residue, as indicated in Fig. 6. The rough phenotype could presumably arise from mutation either at the level of nucleotide sugar synthesis or at some stage in assembly or attachment of the O-antigenic side chains. The pathways of nucleotide sugar synthesis appear to be normal in most rough strains of S. typhimurium (42), a finding which suggests loss of a lipopolysaccharide transferase reaction in these mutants. The site of the enzymatic defect has not yet been established in these cases, but two distinct genetic types of rough mutants have been detected (18). It is interesting to speculate about the function of the lipopolysaccharide. The lipopolysaccharide can account for as much as 5 percent of the dry weight of the cell, and its synthesis clearly involves major expenditure both of energy and of material. Yet loss of the antigenic side chains, or even of a major part of the core structure, appears to have little or no effect on the ability of the organism to survive under laboratory conditions, since the rough and mutant strains grow as well as the wild type does. However, only the wild types, possessing the complete antigenic side chains, are pathogenic. It is possible that the lipopolysaccharide is an important factor in aiding the bacterium to evade host defense mechanisms, such as phagocytosis. Such a role is well established for the capsular polysaccharides of the pneumococci. No mutants have thus far been detected which lack the backbone or lipid portions of the lipopolysaccharide. It may be that these parts of the lipopolysaccharide play an essential role in the physiology of the organism

Carbon Isotopes↗

PubMed1991

Tumor necrosis factor alone does not explain the lethal effect of lipopolysaccharide.

Lethality and tumor necrosis factor production induced by different types of lipopolysaccharide were studied in naive (non-primed) rats during the late phase of endotoxin tolerance. The correlation with antilipopolysaccharide antibodies was also analyzed. No correlation was found between tumor necrosis factor levels and lipopolysaccharide-induced mortality in naive animals. Low-toxicity lipopolysaccharide preparations induced levels of tumor necrosis factor similar to those induced with more toxic types of lipopolysaccharide. Late tolerance was associated with progressively lower levels of lipopolysaccharide-induced tumor necrosis factor and increasing titers of antilipopolysaccharide antibodies after repeated injections of homologous lipopolysaccharide. During late endotonxin tolerance, a direct correlation between the lipopolysaccharide dose and peak tumor necrosis factor serum levels was found. We conclude that since tumor necrosis factor serum levels do not correlate with mortality, tumor necrosis factor alone cannot explain the lethal effect of lipopolysaccharide.

Animals↗

PubMed1990

Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice.

A hypothesis has been proposed by this laboratory that endogenous gut-derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy. Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration. To test this hypothesis liver regeneration was assessed in germ-free euthymic mice that lack the gram-negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin. To complement the germ-free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide-resistant C3H/HeJ mice were also examined. Liver regeneration, quantified by [3H] thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ-free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide-resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals. Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection. Germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration. Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice as compared with conventional euthymic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Helicobacter pylori lipopolysaccharide inhibits acid secretion in pylorus-ligated conscious rats.

To examine the effect of Helicobacter pylori lipopolysaccharide on gastric secretion, the present study was carried out using pylorus ligated conscious rats. Intraperitoneal administration of Helicobacter pylori lipopolysaccharide significantly inhibited gastric acid secretion (4 hr) in a dose-dependent manner (0.033-1.0 mg/rat). The Helicobacter pylori lipopolysaccharide (1 mg/rat)-induced acid inhibition was still observed 8 hr after injection. Gastric acid secretion (4 hr) was compared in the rats that had received intraperitoneal administration of 1 mg/rat dose of Helicobacter pylori lipopolysaccharide or saline alone 24 hr before. There was no significant difference in gastric acid secretion between the saline- and H. pylori lipopolysaccharide-treated rats. These results suggest for the first time that H. pylori lipopolysaccharide may inhibit acid production, and this acid inhibition may be long-lasting. It is also demonstrated that this anti-secretory action of H. pylori lipopolysaccharide has a reversible effect on gastric secretion. All these results suggest that H. pylori lipopolysaccharide might be involved in the low acid secretory function seen in patients with acute H. pylori infection.

Animals↗

PubMed1995

The suppression by lipopolysaccharide of cytochrome P450-dependent renal vasodilation in the rat is mediated by nitric oxide.

The isolated perfused kidney of the rat was used to examine the hypothesis that lipopolysaccharide-induced nitric oxide (NO) production inhibits cytochrome P450-dependent vasodilation. The vasodilator responses to arachidonic acid and bradykinin were examined as the response to arachidonic acid is wholly dependent, and that to bradykinin partly dependent on cytochrome P450 metabolism. In endotoxin-treated rats, the vasodilator response to arachidonic acid was inhibited, and those to bradykinin and acetylcholine were enhanced. Following treatment with phenobarbitone, the inducer of certain isoforms of cytochrome P450 enzymes, the vasodilator effects of all three agonists, especially that of arachidonic acid, were amplified. Lipopolysaccharide inhibited the effect of phenobarbitone on the vasodilator effect of arachidonic acid and bradykinin but enhanced that of acetylcholine. The effect of lipopolysaccharide was antagonized by haemoglobin, a NO antagonist, and N omega-nitro-L-arginine, an inhibitor of NO synthase, suggesting that the inhibitory effect of lipopolysaccharide on arachidonic acid- and bradykinin-induced vasodilation was mediated by NO/NO synthase. N omega-Nitro-L-arginine enhanced vasodilation induced by arachidonic acid while that induced by bradykinin or acetylcholine was reduced, implying that endogenous NO inhibits vasodilator cytochrome P450 metabolites in the rat kidney. Pretreatment with dexamethasone, an inhibitor of inducible NO synthase, resulted in inhibition of the lipopolysaccharide modulation of arachidonic acid-induced vasodilation, suggesting that the inducible NO synthase is the target of the inhibitory effect of lipopolysaccharide. The inhibitory effect of lipopolysaccharide was mimicked by nitroprusside, the L-arginine-independent NO donor, and by L-arginine, the biosynthetic precursor of NO. The effect of L-arginine, but not of nitroprusside, was antagonized by N omega-nitro-L-arginine, suggesting a specific role for NO synthase in the inhibitory effect of lipopolysaccharide in the inhibition of cytochrome P450-dependent vasodilation in the rat kidney.

Acetylcholine↗

PubMed1995

Lipopolysaccharide-induced hepatotoxicity is inhibited by the antioxidant melatonin.

Oxidative damage to the liver of lipopolysaccharide-treated rats was evaluated using four parameters: level of lipid peroxidation, changes in total GSH and GSSG concentrations and hepatic morphology. Bacterial lipopolysaccharide (10 mg/kg b.w.) was injected i.p. either at 6, 16 or 24 h before animals were killed. Lipopolysaccharide increased lipid peroxidation most dramatically when it is injected 6 h before killing. Hepatic total GSH increased after lipopolysaccharide in a time-dependent manner. The highest level of GSSG and largest GSSG/total GSH ratio were also observed in the group of animals injected with lipopolysaccharide 6 h before tissue collection. In a second study, lipopolysaccharide was injected 6 h before the animals were killed, with or without 1 mg/kg b.w. melatonin. Melatonin totally abolished lipopolysaccharide-induced increase in lipid peroxidation, exaggerated the rise in total GSH and reversed the increase in GSSG concentration. The liver showed obvious histological degenerative changes after lipopolysaccharide, effects that were counteracted by melatonin administration. The protection conferred by melatonin is presumably due to its antioxidant activity.

Animals↗

PubMed2005

Tocolytic effect of a Rho-kinase inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery.

OBJECTIVE: The small guanosine triphosphatase RhoA/Rho-kinase cascade has been implicated in uterine contraction. Our purpose was to evaluate the tocolytic effect of a Rho-kinase inhibitor, Y-27632, in lipopolysaccharide-induced preterm delivery in mice. STUDY DESIGN: We used an animal model of lipopolysaccharide-induced preterm delivery in C3H/HeN x B6D2F1 pregnant mice. Y-27632 was delivered continuously through an osmotic pump that was implanted into the peritoneal cavity 6 hours before lipopolysaccharide treatment. The primary outcome was the preterm delivery rate. To further study the possible involvement of this cascade in lipopolysaccharide-induced preterm delivery, we determined the effect of lipopolysaccharide and prostaglandin F2alpha on RhoA activation in mouse myometrial cells and uterine smooth muscle tissues. RESULTS: The rate of preterm delivery for lipopolysaccharide-treated animals was 94.4%. The administration of Y-27632 (1 or 10 mg/kg/d) significantly reduced the preterm delivery rate to 61.1% or 15.8%, respectively. The level of guanosine triphosphate-bound RhoA was increased after the addition of lipopolysaccharide or prostaglandin F2alpha. CONCLUSION: The RhoA/Rho-kinase cascade is involved in lipopolysaccharide-induced preterm delivery, which suggests that Rho-kinase could be used as a new therapeutic target for the prevention of preterm labor.

Amides↗

PubMed2006

Role of p38 and inducible nitric oxide synthase in the in vivo dopaminergic cells' degeneration induced by inflammatory processes after lipopolysaccharide injection.

Accumulating evidences suggest that neuroinflammation is involved in the progressive death of dopaminergic neurons in Parkinson's disease. Several studies have shown that intranigral injection of lipopolysaccharide induces inflammation in the substantia nigra leading to death of tyrosine hydroxylase-positive cells. To better understand how the inflammatory response gives rise to neurotoxicity we induced inflammation in substantia nigra by injecting lipopolysaccharide. The damage of substantia nigra dopaminergic neurons was evaluated by immunohistochemistry, reverse transcription-PCR and Western blot analysis of tyrosine hydroxylase. In parallel, activation of microglial cells, a hallmark of inflammation in CNS, was revealed by immunohistochemistry. Similarly the expression of molecules involved in the inflammatory response and apoptotic pathway was also tested, such as cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), inducible nitric oxide synthase and caspase-11. Tyrosine hydroxylase expression (both mRNA and protein) started to decrease around 3 days post-injection. At the mRNA level, our results showed that the cytokines expression peaked shortly (3-6 h) after lipopolysaccharide injection, followed by the induction of inducible nitric oxide synthase and caspase-11 (14 h). However, inducible nitric oxide synthase protein peaked at 24 h and lasted for 14 days. The lipopolysaccharide-induced loss of substantia nigra dopaminergic neurons was partially inhibited by co-injection of lipopolysaccharide with S-methylisothiourea, an inducible nitric oxide synthase inhibitor. Co-injections of lipopolysaccharide with SB203580, a p38 MAP kinase inhibitor, reduced inducible nitric oxide synthase and caspase-11 mRNA expression, and also rescued dopaminergic neurons in substantia nigra. In summary, this is the first report to describe in vivo the temporal profile of the expression of these inflammatory mediators and proteins involved in dopaminergic neuronal death after intranigral injection of lipopolysaccharide. Moreover data strongly support that lipopolysaccharide-induced dopaminergic cellular death in substantia nigra could be mediated, at least in part, by the p38 signal pathway leading to activation of inducible nitric oxide synthase and caspase-11.

Animals↗

PubMed2001

Effect of E3040, an inhibitor of 5-lipoxygenase and thromboxane synthase, on rat bowel damage induced by lipopolysaccharide.

Intravenous administration of lipopolysaccharide to rats that had been immunized with lipopolysaccharide induced hemorrhagic damage in the large intestine. We investigated the role of 5-lipoxygenase and thromboxane synthase products in the damage of the large intestine induced by lipopolysaccharide. In the large intestine of lipopolysaccharide-immunized rats, intravenous injection of lipopolysaccharide increased the vascular permeability, production of leukotriene B(4), leukotriene C(4)/D(4), thromboxane B(2) and prostaglandin E(2), and also increased the activity of myeloperoxidase, a marker enzyme of neutrophils. Oral administration of E3040 (6-hydroxy-5,7-dimethyl-2-(methylamino)-4-(3-pyridylmethyl)benzothiazole), a novel dual inhibitor of 5-lipoxygenase and thromboxane synthase, at 30 and 100 mg/kg inhibited the increase in vascular permeability induced by lipopolysaccharide in the large intestine. E3040 inhibited the production of leukotriene B(4) and thromboxane B(2) and tended to increase the production of prostaglandin E(2) in the large intestine. Sulfasalazine (500 mg/kg) and prednisolone (10 mg/kg), drugs used for the treatment of inflammatory bowel disease, had no significant effect on eicosanoid production and vascular permeability. These results indicate that E3040 inhibits the production of both leukotriene B(4) and thromboxane B(2) and prevents lipopolysaccharide-induced damage in the large intestine of lipopolysaccharide-immunized rats.

Animals↗

PubMed1999

Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin.

Suppressive effects of naringin on lipopolysaccharide-induced tumor necrosis factor (TNF) release followed by liver injury were investigated. Intraperitoneal (i.p.) treatment with naringin prior to an intravenous (i.v.) challenge of lipopolysaccharide significantly reduced serum TNF levels in a dose-dependent manner and was the most effective when administered 60 min prior to lipopolysaccharide challenge. Treatment with naringin 3 h prior to lipopolysaccharide challenge resulted in complete protection from lipopolysaccharide lethality in D-galactosamine-sensitized mice. Histological estimation revealed that massive cell infiltration followed by severe injury developed in the livers of lipopolysaccharide-treated and D-galactosamine-treated mice unless they had been pretreated with naringin. Appearance of apoptotic cells was also found to decrease by treatment with naringin. Increases in serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase, responsible for lipopolysaccharide-induced liver injury, blocked by naringin administration and the levels were nearly to the normal level. These results indicate that action of naringin is mediated through suppression of lipopolysaccharide-induced TNF production.

Alanine Transaminase↗

PubMed1999

Protective effects of sialyl Lewis X and anti-P-selectin antibody against lipopolysaccharide-induced acute lung injury in rabbits.

The prophylactic effects of selectin inhibitors on lipopolysaccharide-induced acute lung injury were studied in rabbits by using sialyl Lewis X-oligosaccharide and PB1.3, an anti-human P-selectin monoclonal antibody. Lipopolysaccharide-induced acute lung injury resembles that of the acute respiratory distress syndrome, in which there is a decrease in arterial blood oxygen tension (PaO2) and an increase in the difference between alveolar and arterial oxygen tension (A-aDO2). Prophylactic treatment with the selectin inhibitors, sialyl Lewis X-oligosaccharide (55 mg kg(-1) i.v. bolus injection immediately before lipopolysaccharide administration + 36 mg kg(-1) h(-1) i.v. infusion for 4 h) and PB1.3 (5 mg kg(-1) i.v. bolus injection immediately before lipopolysaccharide administration), prevented the lipopolysaccharide-induced impairments in pulmonary gas exchange. In contrast, these agents had no significant effects on lipopolysaccharide-induced systemic hypotension, the decrease in the number of circulating white blood cells and platelets, the decline in blood pH, or the increase in arterial CO2 tension (PaCO2). These results indicate that selectin inhibitors including sialyl Lewis X-oligosaccharide and the anti-P-selectin antibody, PB1.3, attenuate lipopolysaccharide-induced acute lung injury in rabbits. This is the first demonstration that P-selectin is directly involved in the development of lipopolysaccharide-induced impairments in pulmonary gas exchange.

Animals↗

PubMed2000

Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism.

BACKGROUND & AIMS: The bone marrow and the intestine are the major sites of radiation-induced injury. The cellular response to radiation injury in the intestine or bone marrow can be modulated by agents given before irradiation. Lipopolysaccharide is known to be radioprotective in the bone marrow, but its effect on the intestine is not known. We sought to determine if lipopolysaccharide is radioprotective in the intestine and, if so, to determine the mechanism of its radioprotective effects. METHODS: Mice were treated with parenteral lipopolysaccharide or vehicle and then irradiated (14 Gy total body irradiation in a cesium irradiator). The number of surviving intestinal crypts was assessed 3.5 days after irradiation using a clonogenic assay. RESULTS: Parenteral administration of lipopolysaccharide 2-24 hours before irradiation resulted in a 2-fold increase in the number of surviving crypts 3.5 days after irradiation. The radioprotective effects of lipopolysaccharide could be eliminated by coadministration of a selective inhibitor of cyclooxygenase 2. Lipopolysaccharide was radioprotective in wild-type mice but not in mice with a disrupted cyclooxygenase 2. Parenteral administration of lipopolysaccharide resulted in increased production of prostaglandins in the intestine and in the induction of cyclooxygenase 2 expression in subepithelial fibroblasts and in villous, but not crypt, epithelial cells. CONCLUSIONS: Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-dependent pathway.

Animals↗

PubMed1997

Delayed treatment with desulfato-hirudin prevents fibrin formation in lipopolysaccharide-induced shock.

Previous work has shown that pre-treatment with the thrombin inhibitor recombinant desulfato-hirudin prevented fibrin formation and respiratory dysfunction in porcine lipopolysaccharide shock. We examined the effects of delayed administration of recombinant desulfato-hirudin in bacterial lipopolysaccharide shock. Miniature pigs were studied under anaesthesia and ventilation, and received a bacterial lipopolysaccharide infusion (2 microg/kg/h) for 7 h; recombinant desulfato-hirudin was started 1 h after bacterial lipopolysaccharide in 10 animals (bolus 12.9 nmol/kg; continuous infusion 6.5 nmol/ kg/h); 10 randomised control animals received saline instead of recombinant desulfato-hirudin. Fibrin and thrombin-antithrombin complex levels in plasma were significantly lower in bacterial lipopolysaccharide+recombinant desulfato-hirudin animals than in controls. Both groups displayed a similar rise in pulmonary vascular resistance and other parameters of lung dysfunction; only lung tissue wet/dry ratio was lower in recombinant desulfato-hirudin-treated than in control animals. Both groups had similar circulatory alterations. Recombinant desulfato-hirudin interrupted coagulation activation during ongoing bacterial lipopolysaccharide-induced shock in pigs even when administered with a delay of one hour after start of the bacterial lipopolysaccharide infusion. A protective effect of delayed recombinant desulfato-hirudin administration on bacterial lipopolysaccharide-induced acute lung injury and alterations in the systemic circulation could not be demonstrated in this experiment.

Animals↗