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)

Respiratory tract infections are major causes of excessive morbidity and mortality in hospitalized patients. Persons with systemic sepsis have an especially high risk of acquiring these infections, which indicates that their lung antibacterial defenses are compromised. To evaluate the effects of sepsis on pulmonary antibacterial defenses, we injected either saline or 5 mg/kg of Escherichia coli lipopolysaccharide intravenously into Sprague-Dawley rats. Two hours later, the animals were challenged by aerosol inhalation with either Staphylococcus aureus or Pseudomonas aeruginosa. It is known that phagocytic defenses against aerosolized S. aureus challenges are provided solely by the alveolar macrophage; in normal animals challenged with P. aeruginosa, however, an intrapulmonary inflammatory response is elicited. Animals pretreated with endotoxin showed a significant decrease in pulmonary bactericidal activity against S. aureus with 31 +/- 3% bacteria remaining viable at 4 hr compared with 20 +/- 2% in the controls, which indicates a defect in alveolar macrophage antimicrobial activity. After P. aeruginosa challenge, saline-injected control animals developed a marked intrapulmonary inflammatory response and killed greater than 85% of their initial inoculum by 4 hr. By contrast, endotoxin-treated animals failed to recruit neutrophils into the alveoli in response to P. aeruginosa, resulting in a proliferation of this pathogen within the lung (212 +/- 6% bacteria remaining viable at 4 hr). Endotoxin is known to be a potent stimulus for the production of tumor necrosis factor (TNF) by the host. TNF is a potent inflammatory mediator and promotes neutrophil adhesion to the vascular endothelium. In these experiments, serum TNF peaked at 28,390 +/- 7,766 Units/ml. 90 min after intravenous endotoxin. Histopathology of the lungs in these animals showed considerable sequestration of the neutrophils within the pulmonary vasculature. These data show that systemic endotoxin significantly impairs lung host defenses against intrapulmonary bacterial challenges and suggest that TNF-mediated events may play a central role.
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PMID:Endotoxin-induced suppression of lung host defenses. 212 Mar 77

The effects of acute exposure of mice to bacterial lipopolysaccharide (LPS), the endotoxin of gram negative microorganisms, and ozone (O3) have been investigated. Intraperitoneal (ip) administration of 5 mg/kg LPS to CD-1 mice followed by exposure to 15 ppm O3 for 1.5 hr produced synergistic effects as measured by pulmonary edemagenesis and lethality assays. In contrast, ip administration of 0.1-1.6 mg/kg LPS to CD-1 mice over 5 consecutive days, a dose regimen resulting in LPS tolerance, protected against a lethal challenge of 20 ppm O3 for 3 hr. A statistically significant increase in catalase and glutathione peroxidase activity was measured in homogenates of lungs obtained from CD-1 mice receiving a tolerance-inducing regimen of LPS. These results demonstrate that two, distinct toxicologic interactions can occur between O3 and bacterial LPS. Synergism between these agents could explain, in part, the increased susceptibility of O3-exposed animals to respiratory infection with gram negative microorganisms. Protection resulting from LPS-induced increases in pulmonary antioxidant activity provides additional evidence that O3 and, possibly, LPS mediate their toxicity through oxidative mechanisms.
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PMID:Toxicologic interactions between ozone and bacterial endotoxin. 354 25

Chronic respiratory infection with Pseudomonas aeruginosa is a leading clinical problem among patients with cystic fibrosis. Because antimicrobial agents are usually ineffective in eradicating these infections, additional therapeutic or prophylactic measures should be considered. In this study, an experimental guinea pig model of chronic Pseudomonas aeruginosa bronchopneumonia was utilized to determine whether active immunization with lipopolysaccharide (LPS) P. aeruginosa antigen may favorably influence the course of this infection. Experimental pneumonia was established by tracheobronchial instillation of suspensions of microscopic agar beads, which were impregnated with viable P. aeruginosa. After 4 wk of infection, the geometric mean (reciprocal) passive hemagglutinating Pseudomonas antibody titer was 185+/-1.3, and lungs contained 16.8+/-4 x 10(3) colony-forming units Pseudomonas/ml of lung homogenate. Pseudomonas immunization, given prior to a 4-wk infection, resulted in significantly higher passive hemagglutinating titers (474+/-1.4; P < 0.05), lower numbers of viable Pseudomonas in lung tissues (2.4+/-0.6 x 10(3); P < 0.01), and reduced histopathology in lungs. In contrast, providing Pseudomonas immunization to animals 2 wk after pulmonary infection was established, offered no apparent benefit. Likewise, no protection was afforded by prophylactic immunization with a non-Pseudomonas LPS antigen (Escherichia coli J5 vaccine). Using a Raji cell assay, modified to detect circulating immune complexes in vaccinated and infected guinea pig sera, there was no evidence that active immunization increased the frequency of circulating immune complexes in infected guinea pigs. It is concluded that prophylactic immunization with Pseudomonas LPS antigen may confer protection from subsequent Pseudomonas bronchopneumonia, but that immunization during established infection is not beneficial.
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PMID:Active immunization with lipopolysaccharide Pseudomonas antigen for chronic Pseudomonas bronchopneumonia in guinea pigs. 679 29

Using a murine respiratory infection model, we have demonstrated previously that infection with Bordetella pertussis or immunization with a whole-cell pertussis vaccine induced antigen-specific Th1 cells, which conferred a high level of protection against aerosol challenge. In contrast, immunization with an acellular vaccine, consisting of the B. pertussis components detoxified pertussis toxin, filamentous hemagglutinin, and pertactin adsorbed to alum, generated Th2 cells and was associated with delayed bacterial clearance following challenge. In this study, we demonstrated that addition of interleukin-12 (IL-12) either in vitro or in vivo enhanced type 1 T-cell cytokine responses induced with an acellular vaccine. Furthermore, the rate of bacterial clearance in mice coinjected with IL-12 and the acellular vaccine was similar to that observed following immunization with a potent whole-cell vaccine. Analysis of IL-12 secretion by murine macrophages suggested that this cytokine is produced in vivo following B. pertussis infection or immunization with the whole-cell vaccine. IL-12 was detected in the supernatants of lung, splenic, and peritoneal macrophages infected with live B. pertussis or stimulated with heat-killed whole B. pertussis or B. pertussis lipopolysaccharide. In contrast, IL-12 could not be detected following stimulation of macrophages with the bacterial antigens filamentous hemagglutinin, detoxified pertussis toxin, and pertactin, the components of acellular vaccines. Our findings suggest that induction of endogenous IL-12 may contribute to the high efficacy of pertussis whole-cell vaccines and also demonstrate that it is possible to attain these high levels of protection with a less reactogenic acellular vaccine incorporating IL-12 as an adjuvant.
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PMID:Interleukin-12 is produced by macrophages in response to live or killed Bordetella pertussis and enhances the efficacy of an acellular pertussis vaccine by promoting induction of Th1 cells. 894 80

We previously reported the case of a human chronic Bordetella bronchiseptica respiratory infection, due to contact with infected rabbits. Lipopolysaccharides of the human isolates, of one rabbit isolate and of isolate from other origins were analyzed with sera from infected mice, rabbit and human. Antigenicity and length of the lipopolysaccharide molecules varied between isolates. We showed a progressive loss of O-chain during infection, associated with an enhanced susceptibility of the isolates to the bactericidal effect of normal serum. This observation suggests the existence of an intracellular niche which selects for strains with distinct lipopolysaccharide types.
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PMID:Variation in Bordetella bronchiseptica lipopolysaccharide during human infection. 962 69

Respiratory infections which commonly occur in sheep and goats often result from adverse physical and physiological stress combined with viral and bacterial infections. Inevitably, Pasteurella haemolytica pneumonia occurs as a result of these interactions. In this review, we present recent advances in research on the complex etiology of pneumonia involving P. haemolytica. Initially stress, induced by factors such as heat, overcrowding, exposure to inclement weather, poor ventilation, handling and transport is a major predisposing factor. Respiratory viruses including parainfluenza 3 (PI-3) virus, adenovirus type 6 and respiratory syncytial virus (RSV), and to a lesser extent bovine adenovirus type 2, ovine adenovirus types 1 and 5, and reovirus type 1 cause respiratory infections and pneumonia. More importantly these viruses also dramatically increase the susceptibility of sheep and goats to secondary P. haemolytica infection. Primary infection of the lower respiratory tract, with Mycoplasma ovipneumoniae and Bordetella parapertussis can increase the susceptibility of sheep and goats to secondary P. haemolytica infection. It is possible that initial infections with viral or primary bacterial agents break down the antimicrobial barrier consisting of beta defensins and anionic peptides found in epithelial cells, resident and inflammatory cells, and serous and mucous secretions of the respiratory tract. Loss of barrier integrity may release P. haemolytica from its usual commensal status. Once in the lung, P. haemolytica becomes opportunistic. To grow and colonize, P. haemolytica uses extracellular products like O-sialoglycoprotein endopeptidase, neuraminidase and RTX leukotoxin, as well as cell-associated products such as capsular polysaccharide, lipopolysaccharide, outer membrane proteins, proteins involved in iron acquisition and a periplasmic superoxide dismutase. In lambs and kids, pneumonic pasteurellosis can be acute, characterized by fever, listlessness, poor appetite and sudden death. Sheep and goats that survive the acute stage may recover or become chronically affected showing reduced lung capacity and weight gain efficiency and sporadic deaths may occur. This infection is detrimental to sheep and goats throughout the world and flocks and herds of small ranches, dairy operations, or large feedlots are all affected.
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PMID:Pasteurella haemolytica complicated respiratory infections in sheep and goats. 968 40

Growth/differentiation factor 5 is a member of the transforming growth factor beta superfamily, which has neurotrophic and neuroprotective effects on dopaminergic neurons both in vitro and in vivo. Here we investigate the effects of growth/differentiation factor 5 on foetal mesencephalic grafts transplanted into a rat model of Parkinson's disease, and compare them with those of glial cell line-derived neurotrophic factor. Mesencephalic tissue was suspended in solutions containing either growth/differentiation factor 5 or glial cell line-derived neurotrophic factor prior to transplantation into the left striatum of rats with 6-hydroxydopamine lesions of the left medial forebrain bundle. Both proteins enhanced graft-induced compensation of amphetamine-stimulated rotations. Positron emission tomography studies showed that both neurotrophins increased graft-induced recovery of striatal binding of [11C]RTI-121, a marker for dopaminergic nerve terminals. Post mortem analysis at 8 weeks after transplantation showed that both neurotrophins significantly increased the survival of grafted dopaminergic neurons. This study shows that growth/differentiation factor 5 is at least as effective as glial cell line-derived neurotrophic factor in enhancing the survival and functional activity of mesencephalic grafts, and thus is an important candidate for use in the treatment of Parkinson's disease.
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PMID:Growth/differentiation factor 5 and glial cell line-derived neurotrophic factor enhance survival and function of dopaminergic grafts in a rat model of Parkinson's disease. 987 47

It is very surprising that in recent decades, the bacterial infection factor has been so overlooked in the causal treatment of bronchial asthma. Emphasis is put in the viral infection, but the bacterial infection usually associated with it is ignored. In several publications, we have insisted on the importance of the bacterial infection factor in the etiopathogenesis of bronchial asthma. It is alarming that even in the international consensus on its treatment this aspect is overlooked. In the first decades of this century, great importance had already been put on bacterial infection in the triggering of bronchospasm. In this review, we insist on this role of bacterial infection, which comes as a result of our extensive experience in this area, and the fact that in the last 10 years many authors have proven its responsibility at a bronchial mucosa level. In due time, we may be able to prove that the bacterial antigens can potentiate the action of inhalant allergens. Some authors have even proven that the action of these bacterial antigens even more energetically increases the number of intraepithelial dendritic cells in the bronchial mucosa after inhalation of bacterial lipopolysaccharide. Bystander respiratory bacterial infections can also directly modulate T helper 1 and 2 selection parallel to the immune response to inhalant allergens. Recent studies have also proven that in respiratory infection, bacterial antigens hold the main responsibility in the inflammatory and bronchospastic response in the etiopathogenesis of bronchial asthma. Therefore, a consequent treatment of the infection is required, by means of wide spectrum antibiotics, as well as prescription of bacterial immunotherapy, as we have emphasized on other occasions. In conclusion, we must try to cure asthmatic patients and not to maintain them with inhalers and unnecessary corticosteroid therapy, since increasing reactions to corticosteroids are witnessed every day.
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PMID:Bacterial infection as an important triggering factor in bronchial asthma. 1021 51

Low-dose long-term erythromycin treatment has recently been reported to be very effective in patients with chronic respiratory infection and inflammation. This effect of erythromycin was thought to be not antibacterial but anti-inflammatory. However, the exact mechanism of the effect of erythromycin has not yet been clarified. The aims of this study were to investigate the effects of erythromycin on cytokine production and its mechanisms of actions in rat alveolar macrophages. Using rats with or without administration of erythromycin for 3 months, the production of the cytokines tumour necrosis factor-or (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2alpha by enzyme-linked immunosorbent assay and the expression of TNF-alpha and CINC-1 messenger ribonucleic acid (mRNA) by Northern blotting in rat alveolar macrophages were analysed. CINC-1 is the rat counterpart of human interleukin-8, and CINC-2alpha of human macrophage inflammatory peptide-2. Erythromycin reduced cytokine production and secretion when cytokines was induced by lipopolysaccharide treatment. Conversely, erythromycin slightly upregulated the expression of cytokine mRNA. These results suggest that erythromycin inhibits cytokine production and exhibits anti-inflammatory effects by means of a translational and/or posttranslational mechanism.
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PMID:Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages. 1059 99

Pseudomonas aeruginosa is a model for studying opportunistic pathogens that are highly resistant to most classes of antibiotics and cause chronic pulmonary infections. We have developed and adapted a multiplex polymerase chain reaction-based signature-tagged mutagenesis (STM) for high-throughput screening of a collection of 7968 P. aeruginosa mutants in a rat model of chronic respiratory infection. After three rounds of screening, a total of 214 mutants, representing transposition events into 148 open reading frames, were shown to be attenuated in lung infection and were retained for further analysis. As proof of concept supporting this technology, we identified 11 insertions in typical virulence genes such as those coding for pili implicated in motility, attachment and swarming, alginate synthesis and its expression, a mucus transcription regulator, extracellular enzymes such as alkaline protease, esterase and amino peptidase, a rhamnosyl surfactant transferase and a lipopolysaccharide glycosyl transferase. Detailed analysis of the 148 STM mutants, including seven auxotrophs, revealed insertions in 21 of the 26 known gene classes used to characterize sequenced bacterial genomes. We noted that at least 46% of STM mutants identified had insertions in hypothetical proteins or proteins of unknown function and that approximately 40% of all STM mutants had insertions in surface proteins including the outer membrane, the periplasm and the inner membrane. Interestingly, 11 STM mutants attenuated for lung infection were also identified in microarray and transcriptome for quorum sensing and mucoidy production. The remaining 130 mutants were systematically analysed for their capability to express fully known virulence factors. In addition, testing the ability of these mutants to infect alternative model host Drosophila melanogaster revealed 36 STM mutants defective in protease, twitching motility, swimming and swarming. Finally, we identified many genes, the activity of which in respiratory infection was not fully appreciated.
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PMID:In vivo functional genomics of Pseudomonas aeruginosa for high-throughput screening of new virulence factors and antibacterial targets. 1464 75


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