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 in vitro fixation of bacterial lipopolysaccharide (LPS) on the plasma membrane of mechanically or enzymatically isolated hepatocytes from rabbits was studied by immunofluorescence technique. Antisera against LPS from E. coli 026:B6 and 0111:B4 were induced in rabbits. Antibody titers up to 1:1024 were determined by the passive hemagglutination test. There was no immunologic cross reactivity between the two antisera. IgG and IgM were prepared from anti-LPS as well as from normal rabbit serum and conjugated with fluorescein-isothiocyanate. The antibody activity against LPS was localized in the IgM fraction. Hepatocytes were isolated by a perfusion technique without enzymes and with collagenase. LPS binding to the hepatocellular plasma membrane increased proportionally with the LPS concentration in a range between 0.01 and 1.0 mg per ml. The fluorescence pattern of the membrane fixed IgM anti-LPS-antibody at the surface of LPS coated hepatocytes was coarse granular. The in vitro reaction of LPS with hepatocytes was not influenced by the presence of complement. The demonstration of binding sites for LPS on the hepatocellular plasma membrane supports the hypothesis that not only Kupffer cells but also parenchymal liver cells are involved in the hepatic clearance activity for endotoxin.
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PMID:Binding sites for endotoxic lipopolysaccharide on the plasma membrane of isolated rabbit hepatocytes. 39 40

Endothelial cells and macrophages are located within the hepatic sinusoids. These two cell types play an important role in the clearance of bacterially derived lipopolysaccharide from the portal circulation. Our laboratory has previously demonstrated that treatment of rats with lipopolysaccharide results in the accumulation of macrophages in the liver that display properties of activated mononuclear phagocytes. This study was designed to analyze the effects of lipopolysaccharide on hepatic endothelial cells. Female Sprague-Dawley rats were treated with 5 mg/kg of lipopolysaccharide. Macrophages and endothelial cells were isolated from the rats 48 hr later by in situ perfusion of the liver with collagenase and pronase followed by differential centrifugation and centrifugal elutriation. We found that lipopolysaccharide treatment of rats resulted in an increase in the number of both macrophages and endothelial cells recovered from the liver. Using specific monoclonal antibodies and flow cytometry, both macrophages and endothelial cells were found to express cell surface markers for Ia antigen, leukocyte common antigen, CD4 and the macrophage antigen, ED2. Macrophages expressed greater levels of these markers than endothelial cells. Flow cytometric analysis also revealed considerable subpopulation heterogeneity in the endothelial cells in antigen expression, physical characteristics and functional activity. Treatment of rats with lipopolysaccharide decreased expression of cell surface markers on the macrophages but not on the endothelial cells. This may be due to the distinct origin of these cells. To determine whether endothelial cells, like macrophages, were activated by lipopolysaccharide, we examined their ability to produce reactive oxygen intermediates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipopolysaccharide treatment of rats alters antigen expression and oxidative metabolism in hepatic macrophages and endothelial cells. 131 50

Metalloproteinases and their specific inhibitors, believed to play a role in extracellular matrix metabolism, are regulated by inflammatory cytokines. Here we have addressed the question of whether liver, the major site of synthesis of plasma proteinase inhibitors, is also capable of synthesizing the tissue inhibitor of metalloproteinase-1 (TIMP-1). We show at mRNA and protein levels that TIMP-1 is expressed in differentiated human hepatoma cells (HepG2) and that its synthesis is up-regulated by interleukin-6 (IL-6), transforming growth factor beta 1 and phorbol 12-myristate 13-acetate. The physiological role of this phenomenon is underlined by the fact that lipopolysaccharide administration into rats in vivo, as well as IL-6-stimulation of rat hepatocytes in primary culture, also leads to an increase of TIMP-1 mRNA in liver cells.
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PMID:Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in human hepatoma cells (HepG2). Up-regulation by interleukin-6 and transforming growth factor beta 1. 133 Jul 2

The cellular localization of nuclear factor kappa B (NF-kappa B) binding activity in rat liver has been investigated using electrophoretic mobility shift assay on extracts of highly purified hepatocytes and Kupffer cells obtained from liver perfused in vivo with collagenase. Constitutive NF-kappa B binding activity was demonstrated in nuclear extracts of control Kupffer cells, and this was not apparently influenced by injection of lipopolysaccharide (LPS) into rats 24 h before perfusion. In contrast, little nuclear NF-kappa B binding activity was present in hepatocytes from control animals, although there was detectable inactive, inhibitor-bound, NF-kappa B in the cytoplasm. However, nuclear NF-kappa B binding activity was increased in hepatocytes from LPS-treated animals and after in vitro culture of control rat hepatocytes. Thus NF-kappa B binding activity has been demonstrated in highly purified hepatocytes and appears to be inducible both in vivo and in vitro. These findings support a role for NF-kappa B in hepatocyte gene regulation which may be important in the modulation of the hepatic acute phase response.
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PMID:Cellular distribution of nuclear factor kappa B binding activity in rat liver. 144 24

Protein kinase (PK) C has been implicated in a number of cellular events, many of which are also known to be affected by ethanol (ETOH). ETOH intoxication is also known to impair immune function, thereby increasing the host's susceptibility to infection. The purpose of this study was to assess the effect of acute ETOH intoxication on PKC activity and its intracellular distribution in nonparenchymal liver cells following an E. coli lipopolysaccharide (LPS) challenge. The liver was chosen for the study because it is the primary site both for metabolism of ETOH and detoxification of gut derived bacterial products. Catheterized conscious rats were administered saline or ETOH (175 mg/100 g body weight as a bolus followed by a continuous, 7 hr infusion of 28 mg/100 body weight/hr). LPS was injected intravenously (100 micrograms/100 g body weight) 3 hr before the end of the saline or ETOH infusion. Kupffer and endothelial cells were isolated by collagenase-pronase digestion followed by centrifugal elutriation. PKC was assayed after extraction with digitonin containing buffer and partial purification on DE-52 cellulose minicolumns. LPS decreased PKC activity by 69% from control values. Although ETOH infusion alone did not affect PKC activity in Kupffer cells, it completely abrogated the LPS effect. A similar trend was observed for the endothelial cells. No significant differences were observed between groups with respect to the intracellular distribution of PKC. The down-regulation of PKC by LPS may represent a mechanism of functional adaptation of the immunocompetent cells to one of the cytokines, i.e., TNF, whose receptors are down regulated by activation of PKC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute ethanol intoxication prevents lipopolysaccharide-induced down regulation of protein kinase C in rat Kupffer cells. 155 4

We have identified the metalloproteinase inhibitor TIMP-2 as a secreted product of human alveolar macrophages. In contrast to human fibroblasts, TIMP-2 was released from macrophages free of any apparent complexed metalloproteinases. Also in marked distinction to fibroblasts, TIMP-2 secretion from mononuclear phagocytes was subject to modulation by a variety of agents. TIMP-2 was synthesized by macrophages placed in culture under basal conditions in amounts approximately 30% of those secreted by fibroblasts on a per cell basis. The additions of lipopolysaccharide, denatured type I collagen, and zymosan to culture medium each resulted in a dose-dependent and profound decrease in macrophage TIMP-2 protein production and steady-state mRNA levels. In contrast, all of these agents markedly enhanced the biosynthesis of macrophage interstitial collagenase and TIMP-1 as assessed by analysis of identical cell and conditioned media samples. In human fibroblasts, TIMP-2 biosynthesis was unaffected by interleukin-1, tumor necrosis factor-alpha, platelet-derived growth factor, and phorbol ester despite the massive collagenase stimulation induced by each of these agents. We conclude that TIMP-2 is a potentially important mononuclear phagocyte product whose biosynthesis is regulated in a distinct and completely opposite manner to that of collagenase and TIMP-1.
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PMID:Identification of TIMP-2 in human alveolar macrophages. Regulation of biosynthesis is opposite to that of metalloproteinases and TIMP-1. 162 88

Bacterial lipopolysaccharide (LPS) cause airway hyperreactivity in guinea pigs pretreated with metopirone. LPS inhalation resulted in an increase in airway muscarinic reactivity measured by intravenous acetylcholine injection 1-4 h after the inhalation of LPS. The increase of pulmonary capillary permeability was observed 1-24 h after the inhalation of LPS, whereas the increase of leukocytes in bronchoalveolar lavage fluid (BALF) was observed 2 and 24 h after the inhalation of LPS. Increased cells are mainly neutrophil, eosinophil, and macrophage. From the histopathological study, acute mucosal injury and loss of epithelial cilia were observed 1-24 h after the inhalation of LPS. In order to investigate the phlogistic substance in LPS-induced hyperreactivity, the roles of collagenase and elastase were investigated. The activities of both enzymes were elevated 2 h after the inhalation of LPS. The inhalation of collagenase and elastase caused bronchial hyperreactivity and increased pulmonary permeability. The combined administration of prednisolone (10 mg/kg/day) and cyclophosphamide (10 mg/kg/day) for five days decreased LPS-induced hyperreactivity, pulmonary capillary increase, collagenase and elastase activities, and the number of nucleated cells in BALF 2 h after the inhalation of LPS. These results indicate the participation of collagenase and elastase in the onset of LPS-induced airway hyperreactivity in guinea pigs.
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PMID:Participation of collagenase and elastase in LPS-induced airway hyperresponsiveness in guinea pigs. 166 85

We have investigated the surface phenotypic profile of murine lung macrophages in frozen tissue sections, in single-cell suspensions obtained by endobronchial lavage, and in collagenase digests of parenchymal lung tissue, using a panel of monoclonal antibodies directed against pan macrophage markers and antigens present on distinct lymphoid-associated macrophage subpopulations. Our results indicate that lung macrophages from specific pathogen-free (SPF), lipopolysaccharide (LPS) hyporesponsive C3H/HeJ mice are relatively homogeneous no matter what lung tissue compartment they are obtained from. Their predominant surface phenotype was F4/80weak, M1/70-, MOMA-2+, NLDC-145+, MOMA-1+, SER-4+, which resembles the pattern of expression by lymphoid macrophages rather than representative tissue macrophages such as those found in the peritoneal cavity. These results are consistent with the current paradigm that lung macrophages, like lymphoid macrophages, play an important immunoregulatory role within their microenvironment.
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PMID:The surface phenotypic characterization of lung macrophages in C3H/HeJ mice. 178 23

Bacterial endotoxins [lipopolysaccharide (LPS)] are potent immunomodulators, and ethanol is known to depress certain immune defense mechanisms. Thus the combined impact of these two agents on the generation of superoxide anion (O2(-).) by isolated hepatic phagocytic cells was investigated. Ethanol was infused intravenously into rats for 7 h, and Escherichia coli LPS was injected intravenously at 4 h after ethanol administration. Control groups received an equal volume of saline or ethanol alone. Nonparenchymal cells that were composed of endothelial and Kupffer cells and few polymorphonuclear neutrophils (PMN; less than 1%) were obtained after collagenase-pronase digestion. In the LPS-treated rats, the total number of PMN per liver increased significantly. Histological sections of the liver showed PMN infiltration and areas of necrosis after LPS treatment with or without ethanol. In the presence of either phorbol 12-myristate 13-acetate or opsonized zymosan in vitro, Kupffer cells and hepatic PMN from LPS-treated rats generated large amounts of O2(-).. Ethanol intoxication in vitro by these cells to 50%. Ethanol alone (without LPS) had no effect on the production of O2(-).. These studies demonstrate that ethanol intoxication was associated with the downregulation of the LPS-enhanced in vivo priming of hepatic phagocytes to generate O2(-). in vitro and may thus contribute to the enhanced susceptibility of alcoholic subjects to develop an infection.
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PMID:Alcohol-induced downregulation of superoxide anion release by hepatic phagocytes in endotoxemic rats. 185 29

The cytokine neutrophil-activating peptide-1/interleukin-8 (NAP/IL-8) activates neutrophils (PMN) and elicits selective diapedesis of PMN into the extracellular space. The glomerular mesangial cell (MC) is a specialized pericyte that controls glomerular filtration and synthesizes and responds to a variety of cytokines. Because of its location within the glomerulus, the MC is in a pivotal position to orchestrate events underlying immune injury. Since immune-injured glomeruli have been shown to produce NAP/IL-8 activity in vitro, we assessed whether lipopolysaccharide (LPS)- or cytokine-activated MC might be a source of this activity. Pure human MC, devoid of monocyte/macrophage and fibroblast contamination, were grown by explant from collagenase-treated glomeruli. Human recombinant interleukin-1 alpha (IL-1 alpha, 20 ng/ml), IL-1 beta (50 ng/ml), tumor necrosis factor alpha (TNF, 100 ng/ml) and lipopolysaccharide (LPS, 10 micrograms/ml) stimulated release of a neutrophil chemotactic factor from cultured MC. Both concentrated (fivefold) and unconcentrated MC supernatants stimulated directed neutrophil migration under agarose at a level similar to that of the bacterial chemotactic factor, FMLP. In contrast, unstimulated MC-conditioned media and IL-1 alpha, IL-1 beta. TNF and LPS in medium alone did not directly induce PMN migration. Molecular sizing studies using sequential membrane ultrafiltration identified significant TNF-stimulated, MC-derived chemotactic activity in the 3000 to 10000 kD fraction. An anti-NAP/IL-8 monoclonal antibody, 46E5, significantly inhibited PMN chemotaxis stimulated by TNF-stimulated, MC-conditioned media in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine- and LPS-induced synthesis of interleukin-8 from human mesangial cells. 189 76


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