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)

Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia. The major adhesin of A. pleuropneumoniae has previously been identified as a lipopolysaccharide (LPS), and more recently, we demonstrated that high molecular mass LPS were involved in A. pleuropneumoniae adherence to porcine respiratory tract cells. We postulated that immunization with a LPS-based vaccine may confer a protective immunity. The high molecular mass O-polysaccharides obtained after acid hydrolysis and chromatographic separation were conjugated to bovine serum albumin (BSA) as a protein carrier. Groups of mice were injected twice with the following antigen preparations: whole-cell preparation, outer membrane preparation, O-polysaccharide-BSA conjugate, hydrolyzed LPS and phenol/water extracted LPS. A combination of different adjuvants was also used during these immunization procedures to induce a stronger immunological response to the polysaccharide antigen. Two weeks after the second injection, the mice were challenged intranasally with either homologous A. pleuropneumoniae serotype 1 strain or a serotype 5 strain. The highest survival rate, up to 80%, compared to the control groups (P < 0.05), was recorded when the mice were injected twice with 15 micrograms of carbohydrates of O-polysaccharide-BSA conjugate mixed with the saponin-derived adjuvant Quil A. Survival rates of between 60 and 70%, twice those observed in the control groups immunized with PBS, were recorded in mice injected with the O-polysaccharide-BSA conjugate mixed with other adjuvant preparations such as alhydrogel, peanut oil and Freund's incomplete adjuvant. However, the protection induced by the conjugate antigen preparation was serotype specific, because mice challenged with a serotype 5 strain were killed. Taken together, these results confirm the important role of A. pleuropneumoniae LPS in pathogenesis.
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PMID:Evaluation of protective efficacy of an Actinobacillus pleuropneumoniae serotype 1 lipopolysaccharide-protein conjugate in mice. 902 43

Six macrophage cell lines, each derived from a bone marrow macrophage colony grown in soft agar, were established by expansion of the macrophage clones in liquid culture until spontaneous transformation occurred. Four lines originated from the LPS(d) nonresponder mouse strain C3H/HeJ and two from the LPS(n) responder strain CBA/J. The cell lines adhered to plastic and glass surfaces and displayed typical macrophage functions such as phagocytosis and nonspecific esterase activity. Flow cytometry analyses showed that the lines expressed the macrophage surface markers CD11b, CD13, CD32/16, F4/80, and BM8 constitutively. A moderate expression of the adhesion receptor CD11a, but only a very low expression of its ligand CD54, was observed. A minor fraction of the cells in each line constitutively expressed MHC class II antigen, and its expression could be up-regulated in each cell line by treatment with interferon-gamma (IFN-gamma). Secretion of the inflammatory mediators nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) after induction by three bacterial derivatives, heat-killed Salmonella typhimurium (HKS), lipopolysaccharide (LPS), and the Mycoplasma fermentans-derived amphiphilic lipid MDHM, were examined in detail. Not only did the lines differ in the amounts of mediators secreted in response to any one stimulus, but the doses of MDHM or LPS required for 50% maximal induction of NO varied up to 10-fold among the four LPS(d) cell lines, suggesting considerable functional heterogeneity between the clones. Secretion of large amounts of TNF-alpha was induced in all the cell lines by HKS. Although it could be shown that exogenously added TNF-alpha acted synergistically with IFN-gamma to induce NO release from the cell lines, an autocrine role for TNF-alpha during HKS-IFN-gamma induction of NO synthesis could not be substantiated. Neutralization of TNF-alpha with a specific antibody completely blocked NO induction by exogenous TNF-alpha but did not abrogate NO release either by HKS-IFN-gamma-induced cells or by macrophages treated with supernatant from an HKS-IFN-gamma-activated cell line. These results indicate that the clones are arrested in distinct stages of differentiation and retain some properties of normal untransformed macrophages. They should be helpful tools for investigations into macrophage function.
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PMID:Characterization of clonally derived, spontaneously transformed bone marrow macrophage cell lines from lipopolysaccharide hyporesponsive LPS(d) and normal LPS(n) mice. 910 34

The major adhesin of Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, has been previously identified as lipopolysaccharide (LPS). The purpose of the present study was to isolate and characterize A. pleuropneumoniae LPS mutants. Screening of LPS mutants was performed with colony dot and sensitivity to novobiocin. One mutant obtained by colony dot (F19) and one mutant selected for its increased sensitivity to novobiocin (33.1) did not react with a monoclonal antibody against A. pleuropneumoniae serotype 1 O-antigen compared with the parent strain. Mutants F19 and 33.1 did not express high-molecular-mass LPS bands as determined in silver-stained SDS-PAGE gels. The core-lipid A region of mutant 33.1 and of the parent strain had similar relative mobilities and reacted with serum from a pig experimentally infected with the serotype 1 reference strain of A. pleuropneumoniae, while the same region in mutant F19 showed faster migration and did not react with this serum. Use of piglet tracheal frozen sections indicated that mutant F19 was able to adhere to piglet trachea as well as the parent strain, while mutant 33.1 adhered [half as much as] the parent strain. Finally, both LPS mutants were markedly less virulent in mice than the parent strain. Taken together, our observations support the idea that LPS is an important virulence factor of A. pleuropneumoniae.
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PMID:Isolation and characterization of LPS mutants of Actinobacillus pleuropneumoniae serotype 1. 923 94

Mycoplasmas are bacteria which can cause respiratory, arthritic, and urogenital diseases. During the early phase of infection, mycoplasmas usually induce an inflammatory response and a humoral response preferentially directed against their membrane-bound, surface-exposed lipoproteins. In this report, we describe the effects on immune cells of spiralin, a well-characterized mycoplasmal lipoprotein. Purified spiralin stimulated the in vitro proliferation of human peripheral blood mononuclear cells and murine splenocytes. The stimulation pathway was probably different from that followed by Escherichia coli lipopolysaccharide because the effect of spiralin was not abolished by polymyxin B. Comparison of the effects of whole, native spiralin with those induced by proteinase K-digested spiralin or by the C-terminal half of spiralin (peptide p[13.5]T) revealed that the first half of the protein, which contains the lipoylated N terminus, is responsible for the mitogenic activity. In contrast to whole spiralin, proteinase K-digested spiralin did not trigger murine B-cell differentiation and immunoglobulin G and M secretion. Stimulation of human or murine immune cells led to early secretion of proinflammatory cytokines (human tumor necrosis factor alpha and murine interleukin 1 or 6). Spiralin induced the T-cell-independent blastogenesis of murine B cells but did not stimulate T cells. Altogether, our data demonstrate that spiralin possesses potent immunostimulating activity, similar to that reported for lipoproteins of pathogenic gracilicutes (gram-negative eubacteria; e.g., Borrelia burgdorferi OspA and E. coli Braun lipoprotein), and are consistent with the fact that lipoproteins are major antigens during mycoplasma infections.
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PMID:Spiralin, a mycoplasmal membrane lipoprotein, induces T-cell-independent B-cell blastogenesis and secretion of proinflammatory cytokines. 931 43

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

The influence of different induction protocols on the recovery of elicited turkey respiratory macrophages (RM), and on their oxygenation activity and nitric oxide (NO) production was examined. RM were induced in three week old specific pathogen free turkeys with Sephadex G-50, Thioglycollate broth, and an emulsion of incomplete Freund's adjuvant (IFA), supplemented either with Mycoplasma hyorhinis grown in Modified Channock broth (IFA-M. hyorhinis) or with Modified Channock broth (IFA-Broth). The RM were recovered by lavage of the lungs and air sacs and were purified by centrifugation through a Percoll suspension. Their oxygenation activity was evaluated in luminol-enhanced chemiluminescence assays, following stimulation with Zymosan A. The NO production was evaluated by incubating the RM with lipopolysaccharide (LPS) from Salmonella enteritidis for 24 or 48 hours. The number of recovered RM was slightly, but not significantly lower for Sephadex G-50 and IFA-Broth than for Thioglycollate broth and IFA-M. hyorhinis. RM elicited with Sephadex G-50 and IFA-Broth showed a significantly higher oxidative burst response to Zymosan A, compared to the Thioglycollate and IFA-M. hyorhinis elicited RM. Although all elicited RM showed a high NO production upon stimulation with LPS, no significant differences were seen in the NO production of the RM obtained following the different induction treatments. Our results point out that care should be taken when applying elicited RM for in vitro assays, as distinct levels of oxygenation activity were obtained using different induction protocols.
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PMID:Oxygen radicals and nitric oxide production by turkey respiratory macrophages. 969 86

Mycoplasmas are potent macrophage stimulators. We describe the isolation of macrophage-stimulatory lipopeptides S-[2, 3-bisacyl(C16:0/C18:0)oxypropyl]cysteinyl-GQTDNNSSQSQQPGS GTTNT and S-[2,3-bisacyl(C16:0/C18:0)oxypropyl]cysteinyl-GQTN derived from the Mycoplasma hyorhinis variable lipoproteins VlpA and VlpC, respectively. These lipopeptides were characterized by amino acid sequence and composition analysis and by mass spectrometry. The lipopeptides S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-GQTNT and S-[2, 3-bis(palmitoyloxy)propyl]cysteinyl-SKKKK and the N-palmitoylated derivative of the latter were synthesized, and their macrophage-stimulatory activities were compared in a nitric oxide release assay with peritoneal macrophages from C3H/HeJ mice. The lipopeptides with the free amino terminus showed half-maximal activity at 3 pM regardless of their amino acid sequence; i.e., they were as active as the previously isolated M. fermentans-derived lipopeptide MALP-2. The macrophage-stimulatory activity of the additionally N-palmitoylated lipopeptide or of the murein lipoprotein from Escherichia coli, however, was lower by orders of magnitude. It is concluded that the lack of N-acyl groups in mycoplasmal lipoproteins explains their exceptionally high in vitro macrophage-stimulatory capacity. Certain features that lipopolysaccharide endotoxin and mycoplasmal lipopeptides have in common are discussed. Lipoproteins and lipopeptides are likely to be the main causative agents of inflammatory reactions to mycoplasmas. This may be relevant in the context of mycoplasmas as arthritogenic pathogens and their association with AIDS.
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PMID:Structure and specific activity of macrophage-stimulating lipopeptides from Mycoplasma hyorhinis. 974 82

Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for veterinary use in cattle and swine respiratory disease, and is in development for use in poultry mycoplasma air sacculitis. In order to provide an understanding of clinical efficacy, the in vitro interaction of tilmicosin with three types of chicken phagocytes (MQ-NCSU macrophages, monocyte-macrophages, and heterophils) was evaluated. After incubation with radiolabeled tilmicosin, uptake was determined and expressed as the ratio of the cellular (Cc) to the extracellular (Ce) drug concentration (Cc:Ce). Tilmicosin was avidly accumulated by heterophils (Cc: Ce 138 at 4 h incubation vs 32 and 66, respectively, in MQ-NCSU and monocyte-macrophages) with 61 to 88% localized in the lysosomes. Uptake was dependent on cell viability, temperature, and pH, but was not influenced by metabolic inhibitors. However, phagocytosis of Pasteurella multocida and lipopolysaccharide exposure increased tilmicosin uptake by the chicken phagocytes. Upon removal of extracellular tilmicosin, 50% of the intracellular tilmicosin was effluxed within the first 30 min, but after 4 h of incubation in antibiotic-free medium, 30% remained cell-associated. Opsonized P. multocida significantly enhanced the release of tilmicosin from all three types of chicken phagocytes. Tilmicosin uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme, avidin, and beta-glucuronidase) production. Finally, neutrophils were shown to transport and efflux bioactive tilmicosin in a test system measuring both neutrophil chemotaxis under agarose and a bioassay measuring inhibition of bacterial growth in the presence of antibiotic in agar. These in vitro observations of cellular pharmacology suggest a complex interaction between phagocytes and tilmicosin that contribute to clinical efficacy.
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PMID:Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in chicken phagocytes. 977 59

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that appears to play a significant role in the development of neonatal chronic lung disease (CLD). Inflammation and CLD are also associated with respiratory tract colonization with genital mycoplasmas. The possible protective roles of surfactant in mitigating the inflammatory response to these microbes were investigated. Murine RAW 264.7 macrophages were preincubated with an exogenous surfactant and exposed overnight to sterile media, lipopolysaccharide (LPS), Mycoplasma hominis, or Ureaplasma urealyticum. Macrophages released TNF-alpha in response to challenge with LPS, U. urealyticum, and M. hominis in a concentration-dependent fashion. Surfactant suppressed LPS and M. hominis induced TNF-alpha production in a dose-dependent manner but suppressed U. urealyticum-mediated TNF-alpha production only at the higher dose tested. Similar effects were seen in hyperoxia (95% O2). Thus, exogenous bovine surfactant significantly inhibits the production of TNF-alpha by murine macrophages stimulated with genital mycoplasmas and bacterial LPS.
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PMID:Exogenous bovine surfactant suppresses tumor necrosis factor-alpha release by murine macrophages stimulated by genital mycoplasmas. 980 43

The major adhesin of Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, has been previously identified as the lipopolysaccharide (LPS). Experiments in our laboratory have shown that mice immunised with different A pleuropneumoniae serotype 1 LPS preparations were protected against a challenge with a virulent A pleuropneumoniae serotype 1 isolate. The purpose of the present study was to evaluate the protection of pigs against experimental A pleuropneumoniae infection following immunisation with two of these LPS preparations. Groups of five specific pathogen free (SPF) pigs were injected twice with one of the following antigen preparations: detoxified LPS, O-polysaccharide-BSA conjugate, a commercial bacterin, or PBS. Two weeks after the second injection, pigs were challenged intranasally with a virulent A pleuropneumoniae serotype 1 strain. Upon macroscopic examination, fibrino-haemorrhagic pleuropneumonia, compatible with A pleuropneumoniae infection, was observed in one to four pigs in each group. The more extensive lesions were present in control, unimmunised pigs and in animals vaccinated with the O-polysaccharide-BSA conjugate. The highest survival rate was recorded when the pigs had been immunised with detoxified LPS or the commercial bacterin. Taken together, our results suggest that a protection comparable with the one obtained with a commercial bacterin was observed when pigs were immunised with a single class of molecules, detoxified LPS. Most importantly, these results confirm the important role of A pleuropneumoniae LPS in protection against porcine pleuropneumonia. Finally, our results also support the idea that mice are not an appropriate model for the evaluation of porcine pleuropneumonia vaccines.
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PMID:Evaluation of the protective efficacy of Actinobacillus pleuropneumoniae serotype 1 detoxified lipopolysaccharides or O-polysaccharide-protein conjugate in pigs. 983 97


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