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 murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic proline/serine-rich putative SH3 binding domain.
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PMID:Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release. 804 93

Endotoxemia, in man, has been associated with an autooxidative reduction in the bioavailability of polymorphonuclear leukocyte receptors. The location and mechanisms of this phenomena have remained unclear; we investigated the effects of lipopolysaccharide (LPS) on intracellular Fc gamma receptor expression. Polymorphonuclear leukocytes (PMN) were incubated with LPS (10 ng/ml), permeabilized with saponin, followed by measurement of CD64, CD32w, and CD16 (Fc gamma RI, II, III) using 125I-monoclonal antibodies directed against these receptors. Exposure of permeabilized PMN to LPS significantly reduced intracellular Fc gamma receptor expression. PMN isolated from patients with chronic granulomatous disease or myeloperoxidase-specific deficiency did not exhibit this effect. Furthermore, specific inhibitors of components of the PMN oxidative burst (NaN3, 10 mM; L-alanine 30 mM) prevented the LPS-induced oxidative reduction in receptor expression. NADPH oxidase inhibition with diphenyleneiodonium also blocked the effect of LPS on intracellular Fc gamma receptor expression. The effects of LPS on intracellular PMN Fc gamma receptors were reproduced with monophosphoryl lipid A but required a 10 times greater concentration than LPS. Preadherence of PMN on fibronectin or arginine-glycine-aspartate-serine (RGDS), but not laminin, prevented the LPS-induced reduction in oxidative receptor expression. The effects of fibronectin/RGDS were blocked by actinomycin D and cycloheximide. Cross-linkage of intracellular Fc gamma receptors prior to exposure to LPS also prevented the LPS-induced oxidative reduction in receptor expression. These results demonstrate that an important pathophysiologic property of LPS is to induce an intracellular oxidative-derived reduction in Fc gamma receptor expression and that the biologically relevant proteins fibronectin and RGDS ameliorate this effect.
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PMID:Regulation of intracellular polymorphonuclear leukocyte Fc receptors by lipopolysaccharide. 806 31

Autoimmune myocarditis is considered to play a major role in the pathogenesis of dilated cardiomyopathy. A new autoimmune myocarditis model was attained by repeated immunization using murine cardiac C-protein with the immunological adjuvant, Klebsiella pneumoniae O3 lipopolysaccharide. For further analysis of a pathological epitope, the cDNA encoding C-protein was isolated; a fusion protein encoded by part of this cDNA induced myocarditis in SMA mice as well as in three other strains: DBA/1J (H-2q), O20/A (H-2pz1), and SJL (H-2s). The nucleotide sequence and its deduced amino acid analysis revealed that this protein had immunoglobulin-like and fibronectin-like repeats. This study provides a new animal model of autoimmune myocarditis which may shed light on the pathogenesis of dilated cardiomyopathy.
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PMID:Autoimmune myocarditis induced in mice by cardiac C-protein. Cloning of complementary DNA encoding murine cardiac C-protein and partial characterization of the antigenic peptides. 808 44

Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and fibronectin are macrophage-derived mediators thought to be important in the pathogenesis of lung injury, inflammation, and fibrosis. In the present studies, we examined the effects of acute exposure of rats to the pulmonary irritant, ozone (O3), on production of these mediators by lung phagocytes. Cells were isolated from lungs 48 h after exposure of rats to air or O3 (2 ppm, 3 h). We found that cells from O3-exposed rats released 2- to 3-fold more IL-1 and TNF-alpha into the culture medium than did cells from air-exposed rats. These effects were time dependent, reaching a maximum at 2 and 24 h for IL-1, and 2 to 4 h for TNF-alpha. We also found that alveolar macrophages from O3-treated rats produced increased amounts of fibronectin, both alone and in response to transforming growth factor-beta, lipopolysaccharide, and interferon-gamma when compared with cells from control rats. Examination of immunohistochemically stained tissue sections indicated increased IL-1, TNF-alpha, and fibronectin in lungs from O3-exposed animals when compared with control animals. IL-1 and TNF-alpha were localized in lung macrophages, whereas fibronectin was associated with blood vessel walls and the lung interstitium. These results demonstrate that lung phagocyte production of these inflammatory mediators is elevated following O3 exposure and suggest that they may play a role in oxidant-induced pulmonary inflammation and injury.
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PMID:Enhanced production of interleukin-1, tumor necrosis factor-alpha, and fibronectin by rat lung phagocytes following inhalation of a pulmonary irritant. 808 66

Eight healthy volunteers were exposed to purified lipopolysaccharide (LPS) by controlled inhalation. Bronchoalveolar lavage (BAL) 3 hours after exposure revealed a pronounced neutrophilia, increase in lymphocytes, fibronectin concentration, and decrease in alveolar macrophage phagocytosis, as compared to a reference BAL.
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PMID:Lipopolysaccharide (LPS) inhalation in healthy subjects causes bronchoalveolar neutrophilia, lymphocytosis, and fibronectin increase. 811 30

In this study we demonstrate that adherence of peripheral blood mononuclear cells (PBMC) to either plastic or extracellular matrix, such as collagen type I or fibronectin, is a significant stimulus for the induction of both interleukin-8 (IL-8) mRNA and antigen. In addition, adherence of PBMC in the presence of lipopolysaccharide, interleukin-1-beta, or tumor necrosis factor-alpha greatly enhances transcription/translation of IL-8 from these leukocytes. Our findings demonstrate that PBMC adherent to either plastic or physiological surfaces in combination with an inflammatory agonist is both a potent and efficacious signal for the expression and production of the neutrophil chemotactic/activating cytokine, IL-8.
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PMID:Adherence in combination with lipopolysaccharide, tumor necrosis factor or interleukin-1 beta potentiates the induction of monocyte-derived interleukin-8. 821 28

The interaction of the macrophage cell line P388D1 with Pseudomonas aeruginosa in the absence of stimulators or opsonins led to substantial association of bacteria, as judged by visual counting and FACScan assays. This association was observable within 5 min of addition of bacteria, could not be disturbed by exhaustive washing, and occurred with pilus- or flagellum-deficient mutants but not with rpoN mutants, which have been proposed to lack a secondary adhesin. In contrast, specific antibody was capable of causing similar enhancement of bacterial uptake regardless of the rpoN phenotype. Fibronectin stimulated uptake of bacteria with the pilus as an adhesin, and stimulation was observable within 5 min. Both fibronectin-enhanced and antibody-opsonized uptake were susceptible to inhibition by pertussis toxin but not by cholera toxin. The influence of fibronectin on P388D1 cells was distinguishable from that of lipopolysaccharide, which caused substantial morphological changes in cells. Although lipopolysaccharide stimulated bacterial uptake, it actually suppressed fibronectin-mediated enhancement of uptake at high concentrations.
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PMID:Mechanisms of nonopsonic phagocytosis of Pseudomonas aeruginosa. 833 62

Highly metastatic, in vivo-selected cells of RAW117-H10 large-cell lymphoma have been shown to be more resistant than poorly metastatic parental RAW117-P cells to the cytolytic and cytostatic activities of activated macrophages in co-culture experiments. Activated macrophages are known to produce soluble, cytostatic respiration-inhibiting factors, and such activities can be duplicated by interferon-gamma (IFN-gamma) or by combinations of IFN-gamma and Escherichia coli lipopolysaccharide (LPS). Highly metastatic RAW117-H10 cells are more resistant to the cytostatic effects of IFN-gamma and LPS than poorly metastatic RAW117-P cells, and short-term (up to 72 hr) treatment with IFN-gamma and LPS does not change the metastatic potentials of RAW117 cells. We have studied the effects of sequential selection of RAW117-P cells for increased resistance to IFN-gamma and LPS. After 7 to 13 sequential selections, the resulting variant lines were completely refractory to the growth-inhibitory effects of IFN-gamma and LPS and cross-tolerant to macrophage-conditioned medium. The selected variants also completely lost their experimental metastatic potentials and their tumorigenicities after s.c. or i.m. injection. Cytofluorographic analysis indicated reduced cell-surface expression of H-2Kd antigen and fibronectin receptor on the variant cells but no change in surface mu heavy-chain immunoglobulin. The IFN-gamma-selected lines were less adhesive to liver microvascular endothelial cells than the unselected RAW117 cell lines, but were equally sensitive to NK cytolysis by spleen cells. Our results suggest that exposure to certain cytokines can affect the growth and metastatic potential of RAW117 cells and result in the selection of resistant variants with altered biologic properties.
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PMID:Modulating the metastatic potential of murine RAW117 large-cell lymphoma cells by selection for resistance to interferon-gamma. 833 93

The production of collagen-degrading proteases by cultured neonatal rat microglia was examined using an immobilized fibronectin-gelatin matrix coupled to a fluorescent marker and by substrate gel analysis. When microglia were plated onto the surface of the matrix and incubated under resting (nonstimulated) conditions, a small but visible amount of immobilized matrix was degraded. Treatment with lipopolysaccharide (LPS) or interleukin-1 (IL-1) significantly increased the number of microglia demonstrating substrate degradation. Substrate-SDS polyacrylamide gel electrophoresis of samples of supernatants from untreated cultured microglia indicated the presence of a 72 and a 92 kD metalloproteinase with characteristics corresponding to collagenases. Supernatants from untreated astrocyte cultures were shown to have primarily a 72 kD metalloproteinase. Proteinase activity increased on stimulation of the microglia with LPS and IL-1 in a dose-dependent fashion. These results indicate that cultured microglia release active proteases capable of degrading the extracellular matrix in a localized region. The production of proteases by activated microglia may have important physiological and pathophysiological consequences within the restricted extracellular matrix of the CNS.
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PMID:Protease production by cultured microglia: substrate gel analysis and immobilized matrix degradation. 835 Mar 90

A description of new commercial and experimental vaccines for viral and bacterial diseases of cattle can be broadly divided into those used for both beef and dairy cows and those used predominantly in dairy cattle. For both types of cattle, newer and experimental vaccines are directed against several of the important viral (e.g., bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, parainfluenza type 3, and foot-and-mouth disease virus) and bacterial pathogens (e.g., Pasteurella spp., Haemophilus somnus). The viral vaccines include gene-deleted, modified live, subunit, and peptide antigens. Newer bacterial vaccines, particularly those for Pasteurella spp., are composed of either modified-live vaccines or bacterins supplemented with toxoid or surface antigens. Haemophilus somnus vaccine research has concentrated mainly on defining unique surface antigens. Novel dairy cow vaccines would include the lipopolysaccharide-core (J5) antigen approach, which has been used for successful immunization against coliform mastitis. Core antigen vaccines also have reduced calf mortality from Gram-negative pathogens. Staphylococcal mastitis vaccines that contain capsular antigens, toxoids, or the staphylococcal fibronectin receptor are of active research interest. Vaccines against mastitis induced by Streptococcus agalactiae and Streptococcus uberis also are areas of intensive research. Delivery of multiple subunit antigens with optimal immune response induction has led to the investigation of attenuated heterologous viral and bacterial expression vectors such as bovine herpesvirus 1, vaccinia, and Salmonella spp. This discussion also demonstrates that molecular biology is being used to advance bovine vaccine technology.
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PMID:Recent advances in bovine vaccine technology. 840 72


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