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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous lipopolysaccharide, 30 mg/kg, results in rapid systemic hypotension in anesthetized rats. Interaction of lipopolysaccharide with the vascular endothelium and blood borne cells results in the elaboration of cytokines and oxygen-derived free radicals, all of which can be injurious to normal endothelial function. To evaluate endothelial function, superior mesenteric artery rings were isolated from endotoxemic rats just prior to death. Endotoxemia significantly blunted superior mesenteric artery ring vasorelaxations to acetylcholine and to A23187 but not to NaNO2. Contraction of superior mesenteric artery rings from endotoxemic rats induced by U46619 was not altered. Treatment with human superoxide dismutase or U74006F, an aminosteroid, significantly preserved vasorelaxation to acetylcholine and A23187. However, the hydroxyl radical scavenger N-(2-mercaptopropionyl)-glycine did not protect the endothelium. Thus, intravenous lipopolysaccharide can induce endothelial dysfunction in superior mesenteric artery rings. Furthermore, because superoxide dismutase but not N-(2-mercaptopropionyl)-glycine preserves endothelial function, it is likely that superoxide radicals mediate the endothelial dysfunction observed in endotoxemic rats.
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PMID:Splanchnic vascular endothelial dysfunction in rat endotoxemia: role of superoxide radicals. 131 8

Injury to the vascular endothelium and the subsequent inflammatory response are considered prerequisites for the development of atherosclerosis. Platelet-derived growth factor (PDGF) production by and monocyte adhesion to aortic endothelial cells (EC) may participate in this inflammatory process and therefore are two potential targets for control by anti-inflammatory agents. Our previous studies have demonstrated that monocyte adhesion and PDGF production are stimulated by thrombin in EC. Here, we provide evidence that treatment of EC with the anti-inflammatory agent 3-deazaadenosine (c3Ado) effectively abolished thrombin-stimulated PDGF production and monocyte adhesion. c3Ado had no significant effect on either basal monocyte adhesion or constitutive PDGF production. c3Ado was also effective in negating monocyte adhesion induced by other agonists, such as interleukin-1, phorbol 12-myristate 13-acetate (PMA), and lipopolysaccharide. Northern analysis demonstrated that c3Ado significantly reduced thrombin- and PMA-stimulated steady-state levels of PDGF-A chain, PDGF-B chain, and endothelial-leukocyte adhesion molecule-1 (ELAM-1) mRNAs. Nuclear run-on studies demonstrated that a marked transcriptional activation of these genes by thrombin and PMA was abrogated by c3Ado treatment. The transcriptional rate of the alpha-tubulin gene was unaffected by the drug. Antibody binding studies with an anti-ELAM-1 monoclonal antibody 7A9 revealed that thrombin-stimulated EC expression of ELAM-1 was abolished by c3Ado, indicating that the suppression of ELAM-1 expression on EC surface may be a mechanism by which c3Ado interferes with monocyte adhesion. Experiments with the nucleoside transport inhibitor nitrobenzylthioinosine suggested that the transport of c3Ado into EC was required for its inhibitory activity. In addition, L-homocysteine thiolactone was found to potentiate the inhibitory activity of c3Ado, suggesting that the accumulation of intracellular c3Ado homocysteine may be the underlying mechanism by which c3Ado inhibits thrombin-induced EC function. Taken together, these results indicate that c3Ado may prove effective against vascular injury and inflammation through its ability to inhibit induction of both monocyte adhesion and PDGF production.
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PMID:3-Deazaadenosine inhibits thrombin-stimulated platelet-derived growth factor production and endothelial-leukocyte adhesion molecule-1-mediated monocytic cell adhesion in human aortic endothelial cells. 137 93

The mesothelium is a flat epithelial lining of serous cavities that could gate the traffic of molecules and cells between the circulation and these body compartments. The present study was designed to elucidate the capacity of mesothelial cells to express adhesion molecules and chemoattractant cytokines, two fundamental mechanisms of regulation of leukocyte recruitment. Cultured human mesothelial cells express appreciable levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and these were increased by in vitro exposure to tumor necrosis factor (TNF), interferon gamma (IFN-gamma), or TNF and IFN-gamma. Interleukin 1 (IL-1) was a less consistent stimulus for adhesion molecule expression in vitro. Unlike endothelial cells, used as a reference cell population, resting or stimulated mesothelial cells did not express E-selectin and ICAM-2, as assessed by flow cytometry. Analysis of VCAM-1 mRNA by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that mesothelial cells expressed both the seven- and the six-Ig domain transcripts, with predominance of the longer species. Monocytes bound appreciably to "resting" and, to a greater extent, to stimulated mesothelial cells. Monocytes exposed to IFN-gamma and lipopolysaccharide, used as prototypic activation signals, showed increased capacity to bind mesothelial cells. Anti-CD18 monoclonal antibody significantly inhibited binding of monocytes to mesothelial cells, and this blocking effect was amplified by anti-very late antigen 4. Mesothelial cells were able to express the chemotactic cytokines IL-8 and monocyte chemotactic protein 1 at the mRNA and protein levels. These results indicate that mesothelial cells can express a set of adhesion molecules (ICAM-1 and VCAM-1) overlapping with, but distinct from, that expressed in vascular endothelium (ICAM-1, ICAM-2, VCAM-1, E-selectin), and that these are functionally relevant for interacting with mononuclear phagocytes. The regulated expression of adhesion molecules and chemotactic cytokines by mesothelial cells is probably important in inflammatory and immune reactions that involve serous cavities, such as the long-known macrophage appearance and disappearance reactions.
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PMID:Expression of adhesion molecules and chemotactic cytokines in cultured human mesothelial cells. 138 76

Endothelial cell activation antigens may play important roles in immune responses and in inflammation. This report describes the identification and characterization of a monoclonal antibody, named EAA-B, which reacts specifically with human umbilical vein endothelial (HUVE) cells pre-treated with tumour necrosis factor-alpha (TNF-alpha) but not with untreated cells. The expression of the EAA-B antigen on HUVE cells could also be induced by interleukin-1 (IL-1), bacterial lipopolysaccharide (LPS), and phorbol esters but not by interferon-gamma (IFN-gamma). By contrast, EAA-B antigen expression on neonatal foreskin and rheumatoid synovial fibroblasts, whether pre-treated with TNF-alpha or not, was not detectable. Peripheral blood leucocytes and the leukaemic cell lines U937, HL-60, Raji and Molt 4 showed no detectable expression of the EAA-B antigen. Kinetic studies demonstrated that the EAA-B antigen was rapidly expressed, peaked at 6 hr and declined to basal level by 24 hr. Western blotting revealed that monoclonal antibody EAA-B recognized a polypeptide of approximately 80,000-90,000 MW. EAA-B partially blocked the augmented adhesion of HL-60 cells to TNF-treated HUVE cells. However, it failed to inhibit the enhanced binding of peripheral blood leucocytes, U937, Raji and Molt 4 Cells to TNF-treated HUVE cells. In situ, the EAA-B antigen was detected on some vascular endothelium in tonsils, lymph nodes, psoriatic skin and rheumatoid synovium but not in normal non-lymphoid tissues. Interestingly EAA-B antigen is also expressed by B lymphocytes in germinal follicle centres (GFC) of lymphoid tissues. The co-expression of this endothelial activation antigen by GFC B lymphocytes may have significant implications for immune responses and in B-lymphocyte differentiation.
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PMID:Identification of a human endothelial cell activation antigen that is co-expressed by germinal follicle centre B lymphocytes. 139 50

This study explores the in vitro relationship between Shiga toxin-producing Shigella spp. and Escherichia coli and the development of vascular complications in humans following bacillary dysentery. We propose that lipopolysaccharide (LPS; endotoxin) may combine with Shiga toxin to facilitate vascular damage characteristic of hemolytic uremic syndrome. We have examined the direct cytotoxic effects of Shiga toxin and LPS on human umbilical vein endothelial cells (HUVEC) in culture. Shiga toxin alone was cytotoxic to HUVEC, whereas LPS was noncytotoxic at concentrations at or below 10 micrograms/ml. Combinations of LPS with Shiga toxin resulted in a synergistic cytotoxic effect. The synergistic cytotoxic response of HUVEC to Shiga toxin plus LPS was dose dependent for both agents and was maximal at 24 h of exposure. This synergistic response was enhanced by preincubation of HUVEC with LPS. LPS (1 micrograms/ml) alone depressed HUVEC protein synthesis in a transient manner and enhanced the protein synthesis-inhibiting activity of Shiga toxin. The synergistic cytotoxic activity of LPS analogs was as follows, in decreasing order: complete LPS = diphosphoryl lipid A greater than monophosphoryl lipid A greater than deacylated LPS. These results are consistent with a role for Shiga toxin and LPS in the development of hemolytic uremic syndrome at the level of the vascular endothelium in humans.
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PMID:Shiga toxin-associated hemolytic uremic syndrome: combined cytotoxic effects of shiga toxin and lipopolysaccharide (endotoxin) on human vascular endothelial cells in vitro. 154 77

The aim of the present study was to analyse whether an increase in the intracellular free Ca2+ concentration ([Ca2+]i) plays a role as a signal mediating synthesis of nitric oxide (NO) in bone-marrow-derived macrophages, either by stimulating induction of NO synthase or by regulating the activity of the enzyme. Therefore we compared the effects of various synthetic analogues of bacterial lipopeptide and of lipopolysaccharide (LPS) on NO production (assessed as nitrite formation during an incubation for 24 h) and on [Ca2+]i [measured with the fluorescent probe indo-1 (1-[2-amino-5-(6-carboxyindol-2-yl)phenoxy]-2- 2-(2'-amino-5'-methylphenoxy)ethane-NNN'N'-tetra-acetic acid)]. Strongly dissociating effects were evoked on nitrite formation and on [Ca2+]i by the stimuli. LPS was preferentially effective on nitrite formation, whereas the Ca2+ ionophore ionomycin and AlF3 induced increases only in [Ca2+]i. The lipopeptides N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)-(2RS)- propyl]-(R)-cysteinylalanylglycine, N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)- (2RS)-propyl]-(R)-cysteinylseryl-lysyl-lysyl-lysine and (S)-(1,2- dicarboxyhexadecyl)ethyl-N-palmitoylcysteinylseryl-lysyl-lys yl-lysine stimulated both parameters, but the maximal effects on nitrite formation and the shape of the dose-response curves did not parallel the effects on [Ca2+]i. Reduction of extracellular Ca2+ with EGTA significantly inhibited increases in [Ca2+]i, but did not change nitrite formation. Furthermore, NO synthesis in the cytosolic fraction of stimulated macrophages was not affected by Ca2+ over the concentration range 10 nM-2 microM. We conclude that increases in [Ca2+]i are not required for NO production in bone-marrow-derived macrophages. Thus the cellular regulation of NO production strikingly differs from that in the vascular endothelium, brain and adrenal gland.
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PMID:Induction and activity of NO synthase in bone-marrow-derived macrophages are independent of Ca2+. 169 56

Endothelial leucocyte adhesion molecule-1 (ELAM-1) is a recently described endothelial surface glycoprotein which is inducible by interleukin 1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) or bacterial lipopolysaccharide (LPS). Using an immunohistochemical technique and a monoclonal antibody (1.2B6) specific for ELAM-1 we have found marked vascular endothelial expression of ELAM-1 in many cutaneous inflammatory disorders, including allergic contact dermatitis, atopic dermatitis and psoriasis, and in dermal infiltrates associated with benign, premalignant and malignant keratinocyte proliferation. In normal skin, minimal levels of ELAM-1 expression were detected. In psoriasis, double-immunoenzyme staining studies revealed a close spatial relationship between ELAM-1 expression and neutrophil margination, suggesting a functional link. Recombinant human interferon-gamma (30 micrograms) injected intradermally in normal adult human volunteers did not substantially upregulate ELAM-1 in contrast to its marked effect on intercellular adhesion molecule-1 (ICAM-1) expression, indicating that this cytokine is probably not involved in ELAM-1 induction in vivo. These results indicate that ELAM-1 is widely induced in cutaneous inflammation with a time course of expression that is longer than that observed in vitro. As ELAM-1 acts as an adhesion ligand for neutrophils, and perhaps monocytes, the expression of this molecule in cutaneous lesions is likely to be an indication of the ability of vascular endothelium to recruit these cells from the circulation. Furthermore, the cytokine inducibility of ELAM-1 is indirect evidence for functional interactions between perivascular mononuclear cells, other resident cells and the blood vessel wall.
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PMID:Endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in cutaneous inflammation. 170 95

Macrophages and certain tumor cell lines can be induced to synthesize nitric oxide (NO) from L-arginine after stimulation with lipopolysaccharide (LPS) or cytokines. In the present study, we have found that culture medium collected after 24 h from unstimulated rat mesangial cells (MC) contains 6.3 +/- 1.2 microM of NO3-/NO2- (the degradation products of NO). These levels were significantly increased when MC were incubated with LPS (10 micrograms/ml) for 24 h (23.9 +/- 4.1, P less than 0.05). The specific inhibitor of NO synthesis, NG-monomethyl-L-arginine (L-NMMA) completely inhibited LPS-stimulated production of NO3-/NO2-, confirming that the NO3-/NO2- was derived from NO within the MC. Recent studies suggest that endothelium-derived relaxing factor (EDRF) produced by vascular endothelium is also NO, and we have previously shown that both EDRF and NO stimulate increases in MC guanosine 3',5'-cyclic monophosphate (cGMP). Thus we sought to determine whether NO synthesized by the MC could affect cGMP levels within the same cells. After 24-h incubation with LPS (10 micrograms/ml), intracellular cGMP level within the MC was 706.3 +/- 197 (SE) compared with 40.5 +/- 7 fmol/micrograms protein in control MC incubated in media alone (P less than 0.01). The changes in cGMP in response to LPS were inhibited by greater than 90% by L-NMMA. Similar to LPS, incubation of MC with the cytokine gamma-interferon also increased NO3-/NO2- in the culture media and increased cGMP levels within MC. The induction of NO synthesis within MC and the concomitant stimulation of MC cGMP may be important in the modulation of the effects of endotoxemia, as well as inflammation, within the glomerulus.
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PMID:Synthesis and action of nitric oxide in rat glomerular mesangial cells. 171 66

We investigated the mechanism by which leukocytes adhere to the pulmonary and liver microvascular endothelium in a septic murine model. After C57BL/6 mice were intraperitoneally (ip) injected with lipopolysaccharide (LPS), a striking peripheral leukocytopenia occurred as neutrophils accumulated rapidly in the lung and liver. When the anti-Mac-1 monoclonal antibody (mAb) was administered intravenously (iv) 2 hr before the ip administrated LPS, leukocytopenia and neutrophil accumulation in the lung and liver were inhibited significantly at 3 hr after the LPS injection. An immunofluorescence study revealed that Mac-1 expression on leukocytes from LPS-injected mice were greatly increased when compared to that of controls. Additionally, an in vitro assay demonstrated that LPS-activated serum increased neutrophil Mac-1 expression and neutrophil adhesion to the endothelial monolayer and that these phenomena are inhibited by pretreatment of neutrophils with anti-Mac-1 mAb. These results indicate that a marked increase in Mac-1 antigen expression by leukocytes plays a crucial role in striking neutrophil attachment to the vascular endothelium and is likely to be the cause of neutrophil accumulation in the lung and liver during endotoxemia.
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PMID:The anti Mac-1 monoclonal antibody inhibits neutrophil sequestration in lung and liver in a septic murine model. 193 26

In vitro adhesion assays were used to directly compare the adhesion of polymorphonuclear leucocytes (PMN) and T cells to endothelial cells (EC). PMN exhibited lower binding to unstimulated EC than T cells. When EC were stimulated with interleukin-1 (IL-1), tumour necrosis factor (TNF) or bacterial lipopolysaccharide (LPS) there was a large and rapid increase in adhesiveness for PMN which peaked at 4 hr. This had fallen significantly by 24 hr and by 72 hr was not significantly elevated above unstimulated adhesion. The increase in adhesiveness of cytokine-stimulated EC for T cells was smaller and more gradual than for PMN, with adhesion peaking around 8 hr and remaining significantly elevated at 72 hr. In contrast, interferon-gamma (IFN-gamma) enhanced EC adhesiveness for T cells but not for PMN, with maximal T cell EC adhesiveness occurring 24 hr after stimulation. As leucocyte adhesion to vascular endothelium is the first step in diapedesis, differences in PMN and T-cell adhesion to EC may be important in determining the timing and composition of inflammatory infiltrates.
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PMID:T cells and neutrophils exhibit differential adhesion to cytokine-stimulated endothelial cells. 210 85


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