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)

BALB/c mice (ischemia: 31; controls: 15) were studied to investigate the effects of intestinal ischemia on antibody synthesis to peptidoglycan polysaccharide (PGPS), a ubiquitous bacterial antigen found in both gram-positive and gram-negative bacteria. The gut ischemia model was produced by placing a vessel loop around the superior mesenteric vessels for 45 minutes. All animals in the ischemia group had visible gut ischemia. Eighteen animals (58%) in the ischemia group survived to 24 hours and all experienced total recovery of gut viability. Single-cell suspensions of splenic lymphocytes were made. After 5 days of culture with lipopolysaccharide, anti-PGPS immunoglobulin concentrations in culture supernatants were measured by ELISA using high-titer BALB/c anti-PGPS serum as control. The synthesis of immunoglobulin by 10(5) lymphocytes was significantly increased in the ischemia group compared with the controls. These results represent the translocation of bacteria after intestinal ischemia, and this antibody response may be important in resistance to sepsis and multiple organ dysfunction attributed to bacterial translocation.
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PMID:Antibody synthesis to peptidoglycan polysaccharide after ischemic injury of the intestine. 841 Dec 85

Interleukin-1 (IL-1) may be involved in gut permeability to macromolecules and gut glutamine metabolism during endotoxemia. We developed a sensitive radioimmunoassay specific for mouse IL-1 alpha (detection limit of 100 pg/ml, or 5 pM) and measured intestinal levels of IL-1 alpha in response to endotoxin. CD-1 mice (N = 190) were randomized to intraperitoneal (ip) or intravenous (i.v.) lipopolysaccharide (LPS) infusion (15 micrograms/g or 1.5 micrograms/g Escherichia coli 0111:B4 LPS) or saline. Mice were sacrificed at Time 0, 30 min, 1 hr, 2.5 hr, 4 hr, 6 hr, 12 hr, and 24 hr (3 mice/group/time point). Small bowel (SB) and large bowel (LB) were harvested and compared to liver. Duodenum, upper jejunum, midjejunum, terminal ileum, cecum, ascending colon, and sigmoid were analyzed in separate experiments. Tissues were frozen, weighed, and homogenized, the homogenates were centrifuged, and the supernates were assayed for immunoreactive IL-1 alpha. IL-1 alpha was expressed as pg/g wt +/- SEM (lowest detectable amount = 1000 pg/g wet tissue (WT)). SB but not LB from normal controls had constitutively elevated levels of IL-1 alpha (6177 +/- 1640 pg/g WT). LPS ip or i.v. produced lethargy, diarrhea, and a dramatic elevation of IL-1 alpha levels in both SB and LB. In SB, IL-1 alpha was elevated compared to baseline at 1 hr (19201 +/- 626 pg/g WT) and reached a fivefold maximal increase at 2.5 hr (31775 +/- 503 pg/g WT) following 15 micrograms/g ip.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal production of interleukin-1 alpha during endotoxemia in the mouse. 841 68

Endotoxin neutralizing protein (ENP), a recombinant form of the anti-lipopolysaccharide factor that was isolated from amebocytes of the American horseshoe crab, Limulus polyphemus, detoxifies lipopolysaccharide (LPS) both in vitro and in vivo. Using the Limulus amebocyte lysate assay, LPS was detoxified by ENP at a 1 to 1 weight ratio (1:1). When isolated rat aortic rings were preincubated for 16 hr with either LPS or LPS/ENP (1:5), only aortas in the LPS/ENP group contracted normally under norepinephrine stimulation. To show that detoxification of a lethal amount of LPS (18 mg/kg, LD50 at 48 hr) persists in vivo, LPS/albumin (1:1) or LPS/ENP (1:1) mixtures were preincubated (30 min, 37 degrees C) and then injected intravenously into rats. In the 8 hr after injection, LPS/ENP challenged rats, in contrast to their LPS/albumin injected counterparts, had significantly fewer physical signs of acute LPS toxicity (P < 0.001). At 48 hr after challenge, all LPS/ENP treated rats survived (P < 0.01 vs LPS/albumin), and with significantly less weight loss (P < 0.001 vs LPS/albumin challenged survivors). At necropsy, the LPS/ENP group was free of typical LPS-induced gross organ lesions, notably in the liver, spleen, gut-associated lymphoid tissue (GALT), and small intestine. By microscopic examination, lymphocytic necrosis in the spleen and GALT of the LPS/ENP treated survivors was significantly milder than that in the LPS/albumin challenged survivors, although the degree of hepatocellular necrosis and small intestinal enteritis was similar. LPS-neutralizing proteins such as ENP may be useful in treating LPS toxicity.
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PMID:Lipopolysaccharide detoxification by endotoxin neutralizing protein. 841 93

Normal physiological clearance of gut-derived endotoxin lipopolysaccharide [LPS] has been described previously; initially, there is uptake by Kupffer cells (KC), then release of modified LPS, followed by hepatocyte uptake. Previous work in our laboratories indicated that LPS is structurally modified with loss of carbohydrate prior to its release by KC. In this study, we functionally characterize KC modified LPS. KC-modified 125I-LPS was prepared from primary rat KC. Escherichia coli 0127:B8 native 125I-LPS or KC-modified 125I-LPS (40 ng) was incubated for 1 hr with 1 x 10E6 primary hepatocytes. The binding of KC-modified LPS was 4.33-fold higher than native LPS (P = 0.0024). Binding analysis studies were conducted to determine the region of KC-modified LPS responsible for enhanced hepatocyte binding. KC-modified Salmonella minnesota LPS was competed with 100-fold excess native or mutant (Ra, Rc, Rd, or Re) strains of LPS or Lipid A with no decrease to hepatocyte binding. S. minnesota-native 125I-LPS was compared with KC-modified 125I-LPS in a study to assess induction of tumor necrosis factor (TNF)-gamma by rat peritoneal macrophages. Native or KC-modified 125I-LPS (100 ng) was presented to 1 x 10E7 peritoneal macrophages for 6 hr. TNF-alpha was measured in supernatants using the WEHI-164 cytotoxicity assay. Native LPS induced 5.7-fold higher TNF-alpha levels than KC-modified LPS (P < 0.0001). The above data suggest that structural alterations in KC-modified LPS are accompanied by functional alterations resulting in enhanced hepatocyte binding and decreased TNF-alpha release. The latter result implies that an early step in LPS detoxification occurs in the KC in which LPS is modified to prevent elicitation of biologically active cytokines.
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PMID:Lipopolysaccharide (LPS) processing by Kupffer cells releases a modified LPS with increased hepatocyte binding and decreased tumor necrosis factor-alpha stimulatory capacity. 842 4

The production of interleukin-1 (IL-1) by rabbit Peyer's patch M cells populating the follicle-associated epithelium (FAE) was studied. Sorted 5D9+ phagocytic epithelial M cells synthesized IL-1 after stimulation with lipopolysaccharide (LPS) in vitro, as evidenced by the ability of culture supernatants to induce the proliferation of the T-cell line D10.G4.1. Fixed LPS-stimulated M cells were less effective at mediating T-cell proliferation than supernatants from LPS-activated M cells. The magnitude of T-cell proliferation was M-cell concentration dependent, and proportional to the dose of LPS. The M-cell-mediated D10.G4.1 cell proliferation was inhibited > 75% with anti-IL-1 alpha, but < 50% with similar concentrations of anti-IL-1 beta. The results show that M cells secrete IL-1, and suggest the participation of M cells in the delivery of a localized co-stimulatory signal for T-cell and B-cell proliferation in the microenvironment of gut-associated lymphoid tissue (GALT).
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PMID:Follicle epithelial M cells are a source of interleukin-1 in Peyer's patches. 847 33

We studied the effects of supplemental dietary arginine (ARG) on endotoxin-induced bacterial translocation. Mice were fed a 20%-casein diet (control) or a 20%-casein diet supplemented with 2% or 4% ARG and then injected with lipopolysaccharide (1 mg/500 microliters). The incidence of bacterial translocation was noted by the recovery of viable organisms from the mesenteric lymph node (MLN) and spleen. The mortality rates of the mice were 40%, 10%, and 20% in the control group and 2%- and 4%-ARG groups, respectively. Of the surviving mice, bacterial translocation occurred in 100% of the control group, in 56% (MLN) and 56% (spleen) in the 2%-ARG group, and in 36% (MLN) and 25% (spleen) in the 4%-ARG group. Quantitative colony counts and median numbers of viable bacteria were lower (p < 0.05) in the 2%-ARG group and slightly lower in the 4%-ARG group compared with the control group. MLN and spleen weights expressed as a percentage of body weight were heavier (p < 0.05) only in the 2%-ARG group. These results support the concept that bacteria may translocate from the gut to other organs and be a potential source of lethal infection after injury, and that supplementation with 2% or 4% ARG could improve outcome.
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PMID:Arginine-supplemented diets inhibit endotoxin-induced bacterial translocation in mice. 858 May 79

Bactericidal/permeability-increasing protein (BPI) is a neutrophil granule protein with potent bactericidal and lipopolysaccharide (LPS)-neutralizing activities. The purpose of this study was to determine if a human recombinant BPI product, rBPI23, would influence neutrophil (PMN) sequestration into various tissues in a rat burn injury model. Leukosequestration may produce local tissue injury from proteases and high-energy oxygen species released from PMNs. Rats received tracheostomy and venous cannulation, then received 17 to 20% total body surface area full-thickness contact burns and resuscitation with 20 ml, of intraperitoneal saline. Ten mg/kg body weight rBPI23 in saline was given by intravenous injection immediately after burn injury, followed by intravenous doses of 2 mg/kg at 2 and 4 hours. Control animals received intravenous saline only. PMN retention in lung, liver, spleen, gut, skin, muscle, kidney, and brain tissues was determined by removing (before burn injury) and differentially radiolabeling PMNs (111In) and erythrocytes (51Cr), reinfusing cells 4.5 hours after burn injury, and measuring tissue radioactivity 30 minutes later. Edema was estimated by measuring extravasated 125I-labeled albumin in the various tissues, 30 minutes after injection. Peripheral blood PMNS were analyzed for intracellular H2O2 content by flow cytometry using a fluorescent dye that reacts with H2O2. Radioisotope studies demonstrated significant (p < 0.05) leukosequestration into lung, liver, gut, kidney, and skin tissues at 5 hours after burn injury. Tissue edema, manifested by radiolabeled albumin retention, was not observed in any tissues. Postburn PMN deposition in lungs and skin was decreased (p < 0.05) by the immediate administration of rBPI23 after burn injury. Flow cytometry showed increased intracellular H2O2 content in peripheral blood PMNs 5 hours after burn injury (p < 0.05), which was unaffected by administration of rBPI23. Since sequestration of metabolically active PMNs may induce tissue injury, therapies that block leukosequestration after burn injury may improve clinical outcomes by limiting remote tissue injury.
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PMID:Effects of recombinant bactericidal/permeability-increasing protein (rBPI23) on neutrophil activity in burned rats. 865 73

Intestinal mucosal hypoperfusion with subsequent ischemia during endotoxemia might cause a breakdown of the gut barrier with translocation of bacteria and their toxins into the systemic circulation, thus maintaining a "gut-derived" septic state. The aim of this study was to investigate the influence of endotoxin on the microcirculation of intestinal villi, which represent the most vulnerable part of the mucosa. The changes in blood flow and in the diameters of the central villus arterioles located in the distal ileum were monitored in control rats without lipopolysaccharide (LPS) exposure (n=7), and in rats receiving 1.5 mg/kg b.w. LPS (n=7) or 15 mg/kg b.w. LPS (n=7) over 60 min. The blood flow and the arteriolar diameters were determined using in vivo videomicroscopy at baseline, and 60 min and 120 min later. In control animals, no change in blood flow and arteriolar diameters were observed during the entire experiment. Administration of 1.5 mg/kg b.w. LPS reduced the blood flow to 69.5 +/- 9.0% of the baseline value at the end of the study period. This decrease in blood flow was associated with a decrease in the villus arteriolar diameters by 17.4 +/- 2.5% from the baseline values. In animals exposed to 15 mg/kg b.w. LPS, the decrease in villus blood flow at 60 min was 64.8 +/- 10.9% of baseline, and at 120 min 66.9 +/- 12.6% of baseline. The diameters of the villus arterioles were reduced by 11.5 +/- 2.4% and 15.1 +/- 1.7%, respectively. In the control group and in the 1.5-mg/kg LPS group, the mean arterial blood pressure did not change during the entire study period. In the 15-mg/kg LPS group, the mean arterial pressure tended to decrease after 60 min. These data suggest a reduction of villus blood flow due to vasoconstriction in the central villus arterioles during normotensive endotoxmia, which might represent the mechanism for the mucosal ischemia observed in critically ill patients.
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PMID:Effect of endotoxemia on intestinal villus microcirculation in rats. 865 36

Nitric oxide can react with superoxide anion to form peroxynitrite. The resultant free radical can be rapidly protonated to yield even more toxic substances such as hydroxyl radical and nitric dioxide. The generation of either of these free radical species can promote lipid peroxidation and subsequent tissue injury if they are formed in excessive amounts. During sepsis, both nitric oxide synthesis and peroxynitrite production are substantially enhanced in a variety of tissues, effects which favor the development of lipid peroxidation. Consequently, this study was undertaken in conscious rats, to ascertain what effect lipopolysaccharide (LPS) has on inducible nitric oxide synthase expression in the small intestine and to determine whether this is associated with lipid peroxidation or morphologic injury. When examined by Western immunoblot analysis, significantly more inducible nitric oxide synthase immunoreactivity was detected in the ileum than in the jejunum 5 hr after treatment with intraperitoneal LPS (1 and 20 mg/kg). Further, using the thiobarbituric acid assay as an index of lipid peroxidation, it was demonstrated that significantly more thiobarbituric acid reactive substances were present in the ileal mucosa than in the jejunal mucosa after LPS (20 mg/kg) administration. However, LPS (20 mg/kg) resulted in morphologic damage to both segments of the intestinal epithelium. These data indicate that the gut is a target during sepsis and that regional differences exist within the small bowel with respect to induction of nitric oxide synthase and lipid peroxidation following LPS treatment. Thus, while induction of nitric oxide synthase during endotoxic shock may still represent a mechanism of local intestinal damage, it is not necessarily associated with enhanced lipid peroxidation.
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PMID:Effects of lipopolysaccharide on intestinal injury; potential role of nitric oxide and lipid peroxidation. 866 Nov 95

To determine actions of acute intoxication on pathophysiologic responses to trauma, anesthetized and ventilated mongrel pigs received a 20% solution of ethanol (EtOH) by an intravenous (IV group; 2 g/kg, n = 8) or an oral (PO group; 3 g/kg, n = 12 x 60 minutes) route of administration, or the lactated Ringer's vehicle (LR group; n = 12). After 60 minutes, all were subjected to soft tissue injury and 30 to 35% hemorrhage, 60-minute shock, and then resuscitation, with shed blood plus supplemental LR. After 3 days, host defense was challenged with Escherichia coli lipopolysaccharide (LPS); (1 microgram/kg x 30-minutes IV). The supplemental resuscitation was identical (50-53 mL/kg/hours), but posttraumatic acidosis was observed in the IV group and the PO group (base deficit = 4.4 +/- 1.3 and 5.5 +/- 0.9 mEq/L) and not in the LR group. After 3 days, the acid-base equilibrium was restored, but a difference in host defense was unmasked by LPS. In the LR group, LPS-evoked pulmonary vasoconstriction was followed by decreased compliance and ventilation-perfusion mismatch, which was associated at 3 to 5 hours with a base deficit, reduced SVO2, and reduced PO2 (-0.5 +/- 0.2 mEq/L, 46 +/- 1%, 127 +/- 1 mm Hg). These changes were blunted in the PO group (2.0 +/- 0.1 mEq/L, 56 +/- 1%, 183 +/- 4 mm Hg) and potentiated in the IV group (-4.3 +/- 0.5 mEq/L, 40 +/- 2%, 60 +/- 2 mm Hg), even though more fluid was required to maintain systemic arterial and cardiac filling pressures following LPS administration in the IV (40 +/- 6 mL/kg/ hours) versus the LR or PO groups (31 +/- 5 or 23 +/- 3). The PO versus LR differences could not be attributed to enteral nutrition because an isocaloric solution of 50% dextrose had no effect versus LR solution. EtOH caused neutropenia following trauma, relative to LR solution, but the IV versus PO differences could not be discriminated on the basis of neutrophil or lymphocytes counts, nor CD18 receptor expression, nor renal or hepatic dysfunction. However, T4 lymphocytes and cortisol, a nonspecific index of inflammation, were higher for at least 24 hours after trauma with IV, relative to PO or LR. Blood EtOH was similar with IV or PO during resuscitation (100-120 mg/dL), but the kinetics were different prior to trauma. With PO, blood EtOH slowly accumulated to a steady state plateau, the level of which was higher with no anesthesia or no trauma. With IV, blood EtOH peaked at 275 mg/dL and then exponentially declined with a rate that was not influenced to a major extent by trauma or by anesthesia. Therefore: 1) EtOH absorption is impaired during trauma (in part because of reduced gut blood flow); 2) acute EtOH intoxication at the time of trauma altered neutrophils, plasma cortisol, and T4 lymphocytes during recovery and host defense to a superimposed LPS challenge. The apparently favorable effect of PO versus IV EtOH on the response to endotoxemia after trauma probably reflects differences in the kinetics of blood EtOH in the interval before reperfusion but a "first pass" effect (metabolism in the gut or liver) might also explain the data.
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PMID:Acute ethanol intoxication and endotoxemia after trauma. 867 25


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