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)

Unidentified low-molecular-weight factor(s) in serum or nasopharyngeal secretions were known to phenotypically increase the resistance of Haemophilus influenzae type b (Hib) to bactericidal and opsonic antibodies, and resistance was attributed to two hypothetical mechanisms. Serum components generating resistance were studied. Mechanism 1, present in some Hib strains and their capsule-deficient mutants and accompanied by apparent increases in lipopolysaccharide content, was reproduced with a mixture of glucose, lactate, urea, and bicarbonate. Mechanism 2, present only in capsulated Hib and accompanied by increased capsulation, was reported with a mixture of Ca++ and lactate. Hib incubated with these compounds in buffer or grown in serum filtrate was resistant, but Hib grown in conventional media containing the metabolites in serum filtrate was resistant, but Hib grown in conventional media containing the metabolites was not. The resistant phenotype, which resembles Hib in vivo, may depend on nutrient balance as well as the specific factors. Lactate apparently is an important energy source for Hib.
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PMID:Host metabolites that phenotypically increase the resistance of Haemophilus influenzae type b to clearance mechanisms. 201 56

Lead, an immunomodulator and potential human carcinogen, is a major airborne pollutant in industrial environments which poses a serious threat to human health. Despite the wide-spread occurrence of respirable lead particles in the air, and the potential human health risks, effects associated with inhalation of particulate lead on the the lung have been poorly studied. This study was performed to determine whether inhalation of particulate lead oxide (PbO), at a concentration below the currently acceptable air lead standard for occupational exposure, disrupts macrophage (M phi) functions important for maintaining pulmonary immunocompetence. These functions include phagocytosis, production of reactive oxygen intermediates, and the biological activity of tumor necrosis factor-alpha (TNF-alpha). Rabbits exposed to PbO at 30 micrograms/m3 for 4 days (3 hr/day) were sacrificed and their lungs lavaged immediately, 24 hr, and 72 hr after the final exposure. Lactate dehydrogenase (a marker of lung cell damage) and lysozyme activity (a marker of lysosome permeability), measured in the lavage fluid, were significantly increased 24 and 72 hr after exposure. PbO produced neutrophil infiltration nor effects on M phi viability or total numbers. Effects on M phi functions were as follows. Phagocytic uptake of latex particles was reduced with increasing post-exposure time reaching a maximum inhibition at 72 hr. Inhalation of PbO enhanced hydrogen peroxide (H2O2) and superoxide anion radical (O2-) production in a time-dependent manner; effects on H2O2 began at 24 hr and were persistent up to 72 hr. Effects on TNF-alpha release/activity appeared earliest and were persistent up to 72 hr. Immediately and 24 hr after exposure, lipopolysaccharide-stimulated activity of TNF-alpha was depressed by 62 and 50%, respectively; after 72 hr, TNF-alpha release was significantly enhanced compared to control levels. Results demonstrate that the lung is a sensitive target for the toxic effects of inhaled lead. This study provides the first evidence that inhalation of particulate lead, at an occupationally relevant concentration, and in the absence of elevated blood lead levels, alters pulmonary M phi functions critical for lung defense against inhaled antigens. Our findings may have important implications for human health and should be considered when evaluating the health risks associated with inhaled lead.
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PMID:Inhalation of particulate lead oxide disrupts pulmonary macrophage-mediated functions important for host defense and tumor surveillance in the lung. 839 81

Continuous veno-venous hemofiltration (CVVH) has been reported to provide beneficial effects during endotoxic shock. This experiment was designed to determine if selective removal of plasma mediators occurs during CVVH and if plasma concentrations of these mediators are reduced. A swine endotoxic-shock model with three groups was used (lipopolysaccharide (LPS) only (n = 6); LPS followed by CVVH (n = 6); and LPS followed by sham CVVH (n = 4). Plasma and filtrate samples were collected at frequent intervals for 5 h. Lactic acid (LA), eicosanoids [prostacyclin (6-keto PGF1 alpha), thromboxane (TxB2), and prostaglandin E2 (PGE2)] and tumor necrosis factor (TNF) were measured in plasma and filtrate. Plasma concentrations of 6-keto PGF1 alpha, TxB2, TNF, and LA were not significantly different in any group. LA, PGE2, 6-keto PGF1 alpha, and TXB2 concentrations were similar in filtrate and plasma. TNF did not move across the membrane into the filtrate, CVVH, as used in this experiment, did not significantly reduce plasma concentrations of any of these mediators.
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PMID:Efficacy of convective removal of plasma mediators of endotoxic shock by continuous veno-venous hemofiltration. 870 93

Lactate enhances lipopolysaccharide (LPS) sialylation and induction of serum resistance in gonococci by CMP-NANA. To investigate whether the enhancement is due to a direct effect on the sialyltransferase, an improved extraction of the enzyme and a reliable quantitative assay were devised. Gonococci (strain F62) were disrupted in a French pressure cell and the bacterial membranes were extracted for 1 h at 37 degrees C with a detergent, NONIDET (1% v/v). The assay involved sialylation of LPS by CMP-14CNANA and scintillation counting of the labelled LPS after fixing it on filter paper strips by trichloracetic acid (TCA) and washing away unincorporated CMP-14CNANA. It was rapid, reproducible and, although the enzyme preparations contained endogenous LPS, was dependent upon added LPS for maximum activity. At 37 degrees C the rate was constant for up to 5 min and proportional to the concentration of extract in the assay. A wide range of concentrations of lithium-L-lactate did not enhance the activity of the extracted sialyltransferase. At concentrations above 22 microM, it was inhibitory. Pre-incubation of gonococci with lactate enhanced subsequent LPS sialylation and induction of serum resistance by CMP-NANA. Hence, the process whereby lactate enhances the effect of CMP-NANA is separate from the action of CMP-NANA itself. Both processes were inhibited by a sublethal concentration of chloramphenicol, indicating that metabolic events are required. Evidently, the enhancement process does not involve a direct activation of the sialytransferase.
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PMID:Lactate enhancement of sialylation of gonococcal lipopolysaccharide and of induction of serum resistance by CMP-NANA is not due to direct activation of the sialyltransferase: metabolic events are involved. 887 16

The splanchnic region is particularly susceptible to shock. The purpose of this study was to evaluate microdialysis of the liver and small intestine as a monitor of splanchnic metabolic deterioration (elevation of lactate and hypoxanthine) in porcine endotoxic shock. Tonometry of the small intestine was used as a reference. Microdialysis probes (liver, ileum, and artery), tonometer, and pulmonary artery catheter were inserted. Eight animals were given Escherichia coli lipopolysaccharide endotoxin (20 micrograms kg-1 h-1 for 2 h). Five animals served as controls. Measurements were made every half-hour. Three hours after onset of endotoxin challenge, there were significant differences between endotoxin and control groups in intestinal lactate and hypoxanthine, as well as liver lactate, in addition to mucosal pH obtained by tonometry. Lactate elevation in blood was first seen at 4 h, while there was no significant hypoxanthine elevation in arterial blood over 5 h. Hence, data obtained from the splanchnic region became significantly different early, when compared with data obtained from arterial blood. Microdialysis of liver and small intestine as well as intestinal tonometry are sensitive tools for detection of splanchnic metabolic deterioration during endotoxin shock.
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PMID:Splanchnic homeostasis during endotoxin challenge in the pig as assessed by microdialysis and tonometry. 888 84

Tissue destruction during periodontitis is believed to be primarily brought about by leukocyte proteinases. We postulate that oral spirochetes cause discharge of polymorphonuclear leukocyte (PMN) lysosomal enzymes. Effects of Treponema denticola 53-kDa outer membrane protein, lipopolysaccharide (LPS), and peptidoglycan on degranulation of matrix metalloproteinases (MMP)-8 (collagenase) and -9 (gelatinase), cathepsin G, and elastase by human peripheral blood PMNs were studied by specific enzyme assays and Western blot analysis. T. denticola 53-kDa kDa outer membrane protein was found to be a particularly efficient inducer of MMP-8 release. The induction was comparable with that of phorbol myristate acetate, a known inducer of PMN specific granule discharge. All of the treponemal substances, most notably the 53-kDa protein and LPS, induced release of MMP-9, a component of C-type granules. Both collagenase and gelatinase released from PMNs were mostly in active forms. Release of cathepsin G and elastase was also observed with the 53-kDa protein treatment. The other T. denticola substances did not induce release of these serine proteinases. Lactate dehydrogenase was not released from PMNs by the treatments, indicating that the degranulation was specific and not caused by toxic effects of the substances. This was confirmed by transmission electron microscopy of PMNs treated with the 53-kDa protein that showed rapid vacuole formation and cell shape changes but no disintegration of the cells. Thus, T. denticola may participate in the PMN-dependent extracellular matrix degradation during the course of periodontal inflammation by triggering the secretion and activation of matrix metalloproteinases.
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PMID:Membrane components of Treponema denticola trigger proteinase release from human polymorphonuclear leukocytes. 903 54

Peritonitis remains a major problem in peritoneal dialysis. The incidence of peritonitis may be reduced by the use of more "biocompatible" peritoneal dialysis solutions that do not impair local host defense mechanisms, such as occurs with conventional lactate-buffered glucose solutions. In the present study, we investigated the use of bicarbonate and lactate as buffer systems and glucose, amino acids, and glucose polymer as osmotic agents on specific cellular functions of isolated fresh blood monocytes in vitro. The bicarbonate-buffered solutions had a physiologic pH (7.0 to 7.6). Lactate-buffered solutions were tested with a pH between 5.5 and 7.3. RPMI 1640 (Roswell Park Memorial Institute, supplied by Biochrom, Berlin, Germany) and phosphate-buffered saline were used as control mediums. The test solutions were incubated with 200,000 monocytes/mL for 45 minutes followed by a 1:1 mix with RPMI 1640 (with supplements) during a 24- or 4-hour tetrazolium bromide test (MTT test) recovery period. Constitutive and lipopolysaccharide (LPS)-stimulated release of interleukin-1beta (IL-1beta) and IL-6 in the supernatants as parameters of cellular host defense and lactate dehydrogenase concentrations and MTT-formazan production as parameters for cell cytotoxicity were measured. Significantly higher IL-6 and IL-1beta release was found in the bicarbonate-buffered solutions, both under basal conditions and after LPS stimulation, compared with the lactate-buffered solutions (LPS stimulation: 1% amino acids/34 mmol/L bicarbonate, IL-1beta: 1,166 +/- 192 pg/mL; 1.5% glucose/34 mmol/L bicarbonate, IL-1beta: 752 +/- 107 pg/mL; 1.5% glucose/35 mmol/L lactate/pH 5.5, IL-1beta: 174 +/- 51 pg/mL). Some of these differences could even be detected in spent dialysate after a 6-hour dwell in continuous ambulatory peritoneal dialysis patients (n = 10). A lower degree of cellular cytotoxicity (lactate dehydrogenase activity) and better-preserved metabolic activity (MTT test) also were found for the bicarbonate-buffered solutions. Amino acids (1%) proved to be comparable to glucose (1.5%) as an osmotic agent at a neutral pH with regard to LPS-stimulated cytokine release and cytotoxicity. The incubation with a glucose polymer solution (7.5% glucose polymer in phosphate-buffered saline, pH 7.3) resulted in a significantly lowered cytokine release (LPS stimulation: IL-1beta, 69 +/- 19 pg/mL) compared with the other solutions with neutral pH (P < 0.01). These results suggest that bicarbonate as a buffer provided better biocompatibility with regard to mononuclear cytokine release and viability compared with lactate. Amino acids and glucose were equivalent to these parameters at a physiologic pH. The glucose polymer solution, however, was associated with a marked depression of cytokine release.
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PMID:Osmotic agents and buffers in peritoneal dialysis solution: monocyte cytokine release and in vitro cytotoxicity. 929 71

Murine thioglycolate-induced peritoneal macrophages (MPMs) and the murine RAW264.7 macrophage-like cell line (RAW cells) constitutively produce vascular endothelial growth factor (VEGF). VEGF production is increased under hypoxic conditions or after cell activation with interferon-gamma (IFNgamma) and endotoxin (lipopolysaccharide, LPS). In contrast, tumor necrosis factor-alpha is produced only by IFNgamma/LPS-activated cells. Lactate (25 mmol/L) does not increase VEGF production by these cells. However, hypoxia, lactate, and IFNgamma/LPS-activated MPMs express angiogenic activity, whereas normoxic, nonactivated MPMs do not. Lack of angiogenic activity is not due to an antiangiogenic factor(s) in the medium of these cells. Angiogenic activity produced by hypoxia and lactate-treated MPMs is neutralized by anti-VEGF antibody, which also neutralizes most of the angiogenic activity produced by IFNgamma/LPS-activated MPMs. The inducible nitric oxide synthase inhibitors Ng-nitro-L-arginine-methyl ester (1.5 mmol/L) and aminoguanidine (1 mmol/L) block production of angiogenic activity by MPMs and RAW cells. In RAW cells, Ng-nitro-L-arginine-methyl ester and AG block IFNgamma/LPS-activated, but not constitutive, VEGF production, whereas in MPMs, neither constitutive nor IFNgamma/LPS-activated VEGF synthesis is affected. Synthesis of tumor necrosis factor-alpha is also unaffected. In contrast to normoxic, nonactivated MPMs, inducible nitric oxide synthase-inhibited, IFNgamma/LPS-activated MPMs produce an antiangiogenic factor(s). We conclude that VEGF is a major contributor to macrophage-derived angiogenic activity, and that activation by hypoxia, lactate, or IFNgamma/LPS switches macrophage-derived VEGF from a nonangiogenic to an angiogenic state. This switch may involve a posttranslational modification of VEGF, possibly by the process of ADP-ribosylation. ADP-ribosylation by MPM cytosolic extracts or by cholera toxin switches rVEGF165 from an angiogenic to a nonangiogenic state. In IFNgamma/LPS-activated MPMs, the inducible nitric oxide synthase-dependent pathway also regulates the expression of an antiangiogenic factor(s) that antagonizes the bioactivity of VEGF and provides an additional regulatory pathway controlling the angiogenic phenotype of macrophages.
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PMID:Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate, and the inducible nitric oxide synthase pathway. 970 18

Oxidation of low density lipoprotein (LDL) has been recognized as playing an important role in the initiation and progression of atherosclerosis. We recently reported that aged garlic extract (AGE) inhibited LDL oxidation and minimized oxidized LDL-induced cell injury. In this study, the antioxidant effects of AGE were further examined using bovine pulmonary artery endothelial cells (PAEC) and murine macrophages. Lactate dehydrogenase (LDH) release, as an index of membrane injury, and intracellular glutathione (GSH) levels were determined. Oxidized LDL (Ox-LDL) caused an increase of LDH release and depletion of GSH. Pretreatment with AGE prevented these changes. AGE exhibited an inhibition of Ox-LDL-induced peroxides in PAEC. AGE suppressed peroxides in murine Macrophage (J774 cells) dose-dependently. The J774 cells were also incubated with AGE, interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) and nitric oxide (NO) production was measured. AGE inhibited NO production in J774 cells. In a cell free system, AGE was shown to scavenge H2O2 dose-dependently. Our data demonstrate that AGE can protect the endothelial cells from oxidized LDL-induced injury by preventing depletion of intracellular GSH and by removing peroxides. AGE also reduces levels of NO and peroxides in macrophages. These data suggest that AGE is a useful protective agent against cytotoxicity associated with Ox-LDL and NO, and it may thus be useful for the prevention of atherosclerosis and cardiovascular diseases.
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PMID:Aged garlic extract attenuates intracellular oxidative stress. 1037 52

Lactate is released in large quantity from sites of sepsis and inflammation. We asked whether the increased lactate production found in sepsis can be explained by the augmented glycolysis of inflammatory cells. The glycolytic metabolism of rat peritoneal leukocytes was measured following cecal ligation and perforation (CLP) or sham laparotomy. CLP augmented glucose uptake, the pentose phosphate pathway, and glucose oxidation. Lactate output increased from 1.03 +/- 0.05 to 1.20 +/- 0.05 fmol x cell(-1) x min(-1) (P < .001). Total lactate output of peritoneal lavage fluid increased from 7.94 +/- 2.59 to 28.12 +/- 5.60 nmol L x min(-1) (P < .005). The effect of lipopolysaccharide (LPS) on the lactate output of whole blood from 31 critically ill patients was measured. Leukocyte lactate production was calculated by multiple linear regression analysis. Following exposure to LPS, human leukocyte lactate output increased from 0.20 +/- 0.09 to 1.22 +/- 0.14 fmol x cell(-1) x min(-1) (P < .001). This rate of production is so high that it suggests that the lactate output of different tissue beds in sepsis may be affected by their different cell populations and state of activation. This study supports the hypothesis that lactate may be more a product of inflammation than a marker of tissue hypoxia in sepsis.
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PMID:Leukocyte glycolysis and lactate output in animal sepsis and ex vivo human blood. 1038 Nov 54


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