Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of antisera against lipopolysaccharide (LPS) raised by immunization with gram-negative bacteria to prevent LPS toxicity and death from gram-negative bacteremia is well established. To demonstrate conclusively that the protective antibody is specific for LPS, we tested an anti-LPS monoclonal antibody (mAb) in three animal models. 7G is an IgG3 mAb directed against an oligosaccharide side chain determinant of LPS from E. coli 0111:B4. This anti-LPS mAb increased the LD50 of 0111:B4 LPS in mice and protected rabbits against the dermal Shwartzman reaction elicited by 0111:B4 LPS. 7G mAb also protected mice against lethal infection with mucin-enhanced E. coli 0111:B4. Pretreatment with 250 micrograms of 7G increased the LD50 by more than 1.5 logs. These studies prove that oligosaccharide side chain-specific antibody to LPS confers protection against LPS toxicity in vivo and against experimental gram-negative infection. In addition, these studies suggest the potential of anti-LPS monoclonal antibody as therapy for gram-negative infection.
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PMID:An immunoprotective monoclonal antibody to lipopolysaccharide. 620 51

A gastric mucosal mucin receptor has been isolated from the epithelial cell membrane by affinity chromatography on wheat germ agglutinin. The receptor protein displayed an apparent molecular weight of 97kDa and exhibited binding specific to gastric mucin in a concentration-dependent manner. The binding of mucin to the mucosal receptor was inhibited by lipopolysaccharide from H. pylori. The inhibitory effect was proportional to the concentration of lipopolysaccharide up to 30 micrograms/ml, at which concentration a 91% decrease in binding occurred. The results suggest that H. pylori lipopolysaccharide is capable of disrupting the integrity of mucus perimeter of gastric mucosal defense by interfering with epithelial cell-mucin binding.
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PMID:Inhibition of gastric mucosal mucin receptor by Helicobacter pylori lipopolysaccharide. 751 19

The interaction of lactoferrin with Actinobacillus actinomycetemcomitans was examined in a 125I-labeled protein binding assay. The binding of human and bovine lactoferrins reached maximum within 1 h. Lactoferrin binding to the bacterium was pH-dependent and reversible. Scatchard analysis indicated the existence of two different types of binding sites on the bacterium, one with a high affinity constant k alpha approximately 8.8 x 10(-7) M) and the other with a low one (k alpha approximately 1.8 x 10(-6) M). Bacteria in the exponential phase of growth showed higher binding than cells in the stationary phase. Bacteria grown in medium containing serum and/or lysed erythrocytes bound lactoferrin to a lesser extent. Heat-inactivated serum, lysed erythrocytes and other proteins such as mucin and laminin inhibited lactoferrin binding to A. actinomycetemcomitans in a competitive binding assay. Sodium dodecyl sulfate polyacrylamide-gel electrophoresis and Western blot analysis of the cell envelope as well as the outer membrane of A. actinomycetemcomitans revealed lactoferrin-reactive protein bands at 29 kDa and 16.5 kDa. The 29-kDa band displayed a heat-modifiable lactoferrin-reactive form with a molecular weight of 34 kDa. Neither proteinase K-treated cell envelope nor lipopolysaccharide of this bacterium showed reactivity with lactoferrin. These data suggests a specific interaction of lactoferrin with outer membrane proteins of A. actinomycetemcomitans.
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PMID:Lactoferrin interaction with Actinobacillus actinomycetemcomitans. 764 71

1. Convincing evidence now exists that infection with H. pylori plays a major role in the pathogenesis of gastric disease. Having a niche bordering two major perimeters of mucosal defenses, the bacterium apparently exerts its detrimental effect on the mucus layer as well as the gastric epithelium. Therefore, gastroprotective agents capable of counteracting these detrimental effects of H. pylori are gaining importance in the treatment of gastric disease. 2. The colonization of gastric mucosa by H. pylori involves specific glycolipid receptors bearing acidic substituents, a process inhibited by gastric sulfomucins. Two antiulcer agents bearing sulfated sugar groups have been demonstrated to possess the ability to interfere with H. pylori colonization process. These are sucralfate and sulglycotide. The two agents are also potent inhibitors of H. pylori glycosulfatase activity directed against indigenous mucosal defenses. 3. A variety of extracellular enzymes such as proteases, lipases and phospholipases, elaborated by H. pylori cause the weakening of the integrity of gastric mucus coat and render the underlying epithelium vulnerable to noxious luminal contents. Among the most potent agents capable of countering the proteolytic activity of H. pylori are nitecapone, ebrotidine and sulglycotide, while ebrotidine and sulglycotide were found to be most effective inhibitors of H. pylori lipolytic activities. 4. The gastric epithelial integrity is compromized by the H. pylori cell-wall lipopolysaccharide untoward effect on the epithelial surface receptors. The interference of the lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding.
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PMID:Gastroprotective agents in mucosal defense against Helicobacter pylori. 783 26

1. A receptor for mucin was isolated from the solubilized gastric epithelial cell membrane by affinity chromatography on Sepharose-bound wheat germ agglutinin. 2. The receptor protein displayed a molecular weight of 97 kDa and exhibited specific affinity towards mucin-coated surfaces. The optimum for mucin binding occurred at 60-100 micrograms/ml, while the values for the receptor were 2.0-3.1 micrograms/ml. 3. The mucin binding to the receptor was susceptible to Helicobacter pylori lipopolysaccharide which caused maximum inhibition of 91% at 30 mu/ml. This inhibitory effect of the lipopolysaccharide was abolished by a gastroprotective agent, sulglycotide. 4. The effect of sulglycotide was dose dependent and at 50 micrograms/ml produced a 94% restoration in receptor-mucin binding. Furthermore, sulglycotide was also capable of enhancing (97%) the mucin binding to its receptor in the absence of the lipopolysaccharide. 5. The results demonstrate that H. pylori through its lipopolysaccharide interferes in the interaction of mucin with gastric epithelial surfaces and that a gastroprotective agent, sulglycotide, counteracts this effect, and hence is capable of preventing the loss of mucin coat continuity occurring with H. pylori infection.
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PMID:Inhibition of gastric mucosal mucin receptor by Helicobacter pylori lipopolysaccharide: effect of sulglycotide. 783 46

Mucus hypersecretion is a prominent response of the airways to bacterial infections. Recent findings showed that bacterial endotoxin, a lipopolysaccharide complex released from the bacterial cell wall, was able to induce at least one component of the hypersecretory response, i.e., an increase in the amount of stored epithelial mucosubstances (1, 2). The goal of the present study was to determine whether endotoxin also was capable of increasing mucosubstance release from cells. Based on evidence that human mucin antibodies A10G5 and B6E8 cross-reacted with rat mucin-like molecules, we used the antibodies in enzyme-linked immunosorbent assays (ELISA) to compare mucin concentrations in bronchoalveolar lavage (BAL) fluid from endotoxin-treated and control rats. Results showed that endotoxin treatment increased the amount of released mucin over that in controls 1.5-fold at 96 h and 2.5-fold at 168 h after instillation. Thus, these studies have defined the previously detected mucosubstances as mucin-like molecules and showed that endotoxin increases their release from, as well as their storage in, rat airway epithelium. Concurrent increases in storage and release suggest that endotoxin also stimulates mucin synthesis and/or stability.
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PMID:Concurrent increases in the storage and release of mucin-like molecules by rat airway epithelial cells in response to bacterial endotoxin. 787 97

Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis. 801 61

A hemagglutinin with a high specific activity against trypsinized rabbit erythrocytes was identified in plasma of the freshwater crayfish Pacifastacus leniusculus. The activity of this crayfish hemagglutinin could be inhibited by sialoglycoproteins such as porcine stomach mucin, bovine submaxillary mucin, fetuin, and ovalbumin. However, the involvement of sialic acid in its binding specificity could not be unambiguously proven. Furthermore, the hemagglutinating activity in the crayfish plasma could be specifically inhibited by lipopolysaccharide from E. coli K-235, which might indicate a recognition role for this hemagglutinin. This hemagglutinin, which accounts for less than 0.01% of the total plasma protein, was purified to near homogeneity using affinity chromatography on a Fetuin-Sepharose 4B column. The molecular mass of the unreduced protein as revealed by sodium dodecyl sulphate electrophoresis in polyacrylamide gel was found to be 420,000 Da. Upon reduction with dithiothreitol the hemagglutinin dissociated to several subunits with masses ranging from 65,000 to 80,000 Da. Affinoblotting with peroxidase labelled lectins indicated that the hemagglutinin was likely to be a glycoprotein.
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PMID:Isolation and characterization of a hemagglutinin with affinity for lipopolysaccharides from plasma of the crayfish Pacifastacus leniusculus. 827 93

Mucous (goblet) cell proliferation and hypersecretion of airway mucus are important characteristics of human respiratory disorders, especially chronic bronchitis and cystic fibrosis. These changes in secretory patterns also occur in animals experimentally exposed to chemical irritants such as ozone (O3), sulfur dioxide (SO2), and cigarette smoke. The cellular and molecular mechanisms involved in irritant-induced mucous cell metaplasia (MCM; transformation of airway epithelium, normally devoid of mucous cells, to a secretory epithelium containing numerous mucous cells) are still unclear. We used two experimental models of toxicant-induced MCM in rat airways to study the cellular and molecular changes that occur during the development of this respiratory tract lesion. MCM can be induced in the nasal transitional epithelium of rats by repeated exposure to ambient levels of ozone. In addition, MCM can be induced in the tracheobronchial airways of rats repeatedly exposed to endotoxin, a lipopolysaccharide-protein molecule found in the outer walls of Gram-negative bacteria. The pathogenesis of ozone- or endotoxin-induced MCM has been partially characterized using a variety of morphometric and histochemical techniques. Toxicant-induced changes in the numbers and types of airway epithelial cells have been estimated using morphometric methods designed for estimating the abundance of cell populations. Nasal pulmonary airway tissues are also processed for light microscopy and stained with Alcian Blue (pH 2.5)/Periodic Acid Schiff (AB/PAS) for detection of acidic and neutral mucosubstances (the specific glycoprotein product of mucous cells), respectively, within the tissue. Computerized image analysis is used to quantitate the amount of the stained mucous product within the airway epithelium. To better characterize the molecular and cellular events in the pathogenesis of ozone- or endotoxin-induced MCM in the rat airway epithelium, we are conducting studies to determine when, and in which epithelial cells, the mucin gene is expressed after exposure to the toxicant. In these studies, rats undergo single or repeated exposures to ozone or endotoxin and are then sacrificed immediately or a few days after the end of the exposures. Airway tissues are microdissected from specific regions of the exposed respiratory tract, and changes in mucin core polypeptide mRNA are evaluated by Northern analysis using human and rat mucin cDNA. In future studies using in situ hybridization, we will establish when, and in which epithelial cells, the expression of high molecular weight airway mucin is initiated in response to ozone or endotoxin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ozone- and endotoxin-induced mucous cell metaplasias in rat airway epithelium: novel animal models to study toxicant-induced epithelial transformation in airways. 851 71

1. H. pylori infection causes the loss of mucus coat continuity and its patchy appearance. Here, we present evidence that the bacterium, through its cell wall lipopolysaccharide, disrupts the interaction between mucin and its mucosal receptor, and that ebrotidine is capable of counteracting this process. 2. The receptor for mucin, isolated from the solubilized gastric epithelial cell membrane by affinity chromatography on Sepharose-bound wheat germ agglutinin, displayed a molecular weight of 97 kDa and exhibited specific affinity towards mucin-coated surface. 3. The mucin binding to the receptor was susceptible to the inhibitin by H. pylori lipopolysaccharide and reached a maximum of 91%. This effect of the lipopolysaccharide was counteracted by ebrotidine, which caused a dose-dependent relief of the lipopolysaccharide inhibitory effect with maximum restoration in mucin-receptor binding of 51% at 60 microliters/ml ebrotidine. 4. The results show that H. pylori, through its lipopolysaccharide, is capable of disrupting the integrity of mucus perimeter of gastric mucosal defense and that antiulcer agent, ebrotidine, counteracts this untoward effect.
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PMID:Inhibition of gastric mucosal mucin receptor by H. pylori lipopolysaccharide: effect of ebrotidine. 869 Feb 45


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