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

We have examined the lipopolysaccharide (LPS) induced release of interleukin 1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha), in EDTA or heparin anticoagulated whole blood, from persons with high or low levels of high density lipoprotein (HDL), incubated at 37 degrees C for up to 20 h. In general, 100 ng LPS/ml gave two to twenty times higher responses than 1 ng LPS/ml, and heparin ten to hundred times higher than EDTA. The release of IL-8 was significantly higher in persons with high HDL, and was correlated with HDL, and inversely correlated with triglycerides and sCD14. The release of IL-1 beta, IL-6 and TNF-alpha was correlated with total cholesterol at medium doses of LPS (100 ng/ml), and inversely correlated with lipopolysaccharide-binding protein (LBP) at low doses of LPS (1 ng/ml). Serum levels of LBP were higher in persons with HDL, although not significantly. These results show LPS responsiveness of pro-inflammatory cytokines in whole blood from persons with high and low levels of HDL to be different, presumably of importance in inflammation and atherogenesis.
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PMID:LPS induced release of IL-1 beta, IL-6, IL-8 and TNF-alpha in EDTA or heparin anticoagulated whole blood from persons with high or low levels of serum HDL. 877 74

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are major mediators of sepsis and multiple organ failure. Serum-mediated macrophage activation requires lipopolysaccharide (LPS) and its serum binding protein, lipopolysaccharide binding protein as a ligand for the receptor CD14. This study was designed to determine whether cytokines participate in regulation of serum-mediated LPS activation. Rat macrophages were stimulated with LPS with and-without TNF-alpha or IL-1 beta and activation was determined by detection of TNF-alpha by specific enzyme-linked immunosorbent assay or TNF-alpha mRNA by Northern blot analysis. The addition of TNF-alpha but not IL-1 beta, in the presence of serum, leads to potentiation of macrophage activation after LPS stimulation. This effect could be specifically inhibited by neutralization of LPS with polymyxin B or an antibody against TNF-alpha. This study shows that LPS and TNF-alpha synergize to potentiate serum-mediated macrophage activation. These results demonstrate another element of the control mechanism of cytokine secretion following macrophage activation in sepsis.
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PMID:Lipopolysaccharide and tumor necrosis factor-alpha synergy potentiate serum-dependent responses of rat macrophages. 879 55

The interacting cellular and molecular systems which we classify as immunity and inflammation evolved to protect the organism from exogenous parasites including viruses and bacteria. Cytokines play a pivotal, but paradoxical, role both in immunity and inflammation. These local peptide hormone-like molecules form a major arm of the organisms, defenses against infectious microorganisms but they are also implicated as potent mediators of the pathology of infectious diseases. The apparently lethal effects of interleukin-1 and tumor necrosis factor in experimental septic shock testify to the latter. In the current paradigm, cytokine induction, as a protective or pathological mechanism, is a direct response to the presence of infectious microorganisms. Evidence is now accumulating that cytokines play a much more complex role in the interplay between exogenous microorganisms and the host. For example, it has been established that viruses have evolved pro-active methods of subverting the cytokine network by producing: (i) soluble cytokine receptors which bind and inactivate cytokines, (ii) immunomodulatory cytokine homologues, and (iii) ICE inhibitors. The possibility exists that the major role of these 'viral cytokines' is to neutralize certain host responses. Recent cytokine transgenic knockouts demonstrate that the normal benign response to commensal gut microflora becomes a lethal inflammatory state in the absence of the cytokines interleukin 2 or interleukin 10. The human body contains an enormous number of microorganisms which constitute the normal microflora. It is estimated that the average human contains 10(13) eukaryotic cells but 10(14) bacteria. We propose that the ability of the multicellular organism to live harmoniously with its commensal microflora must depend on mutual signalling involving eukaryotic cytokines and prokaryotic cytokine-like molecules. Such interactive signalling sets up non-inflammatory cytokine networks in tissues which form the background on which responses to infectious microorganisms must be built and related. The capacity of bacteria to induce cytokine synthesis was believed to be due to a small number of components, such as lipopolysaccharide (LPS), which is only active as a complex with host factors (lipopolysaccharide binding protein and CD14). However, it is now clear that bacteria contain and produce a large number of diverse molecules which can selectively induce the synthesis of both pro-inflammatory and immunomodulatory/anti-inflammatory cytokines. Many toxins are potent inducers of cytokine release or synthesis and some can inhibit LPS-induced cell activation. We have introduced the term bacteriokine to describe these bacterial cytokine inducers. The question that has to be addressed therefore is - who controls the cytokine network (eukaryotic or prokaryotic cells) and how is it controlled? It is proposed that an understanding of this question will bring with it an understanding of how to control the pathological inflammatory response and may allow the development of truly effective anti-inflammatory agents.
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PMID:Microbial/host interactions in health and disease: who controls the cytokine network? 891 90

One way prokaryotes respond to environmental stresses is by modifying selected outer membrane components. Iron, in the form of hemin, has been shown to be a significant regulator of Porphyromonas gingivalis growth and virulence and of the expression of outer membrane proteins and lipopoly saccharide. Since lipopoly saccharide has profound effects on host immune cells, this study compared the effect of hemin-restricted and hemin-normal P. gingivalis growth conditions on lipopolysaccharide priming of N-formylmethionyl-leucyl-phenylalanine-induced superoxide generation by human neutrophils. P. gingivalis was grown in a chemostat under normal (5 micrograms hemin/ml) and hemin-restricted (0.08 microgram hemin/ml) conditions. Purified lipopolysaccharide from both P. gingivalis normal and hemin-limited environments increased N-formylmethionyl-leucyl-phenylalanine-induced superoxide release by neutrophils in a dose-dependent manner. Lipopolysaccharide isolated from the hemin-normal conditions was a significantly more potent neutrophil priming agent than the lipopolysaccharide isolated from hemin-restricted conditions. Addition of normal human serum enhanced the priming effect of both lipopolysaccharide preparations; this effect, however, was more evident with the hemin-normal lipopolysaccharide. Further, this enhancing effect of serum was partly reduced in the presence of antibodies raised against the serum lipopolysaccharide-binding protein. The differences in the biological activity of the two lipopolysaccharide preparations could be associated with structural differences detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. These results indicate that hemin availability affects regulation of an aspect of P. gingivalis virulence, lipopolysaccharide-human neutrophils priming. The reduced capacity for neutrophil priming by hemin-restricted lipopolysaccharide appears to be related to lipopolysaccharide-neutrophil interactions and not to serum factors Targeting bacterial cell-surface components involved in hemin transport might be effective therapy for P. gingivalis-associated periodontal diseases.
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PMID:Lipopolysaccharide isolated from Porphyromonas gingivalis grown in hemin-limited chemostat conditions has a reduced capacity for human neutrophil priming. 902 57

Two crucial mediators of monocyte activation by lipopolysaccharide (LPS) are the acute phase plasma factor, lipopolysaccharide binding protein (LBP) and cell-surface-expressed CD14. Whether macrophage (M phi) recognized and respond to LPS in a similar manner is unknown. Here we show that human monocyte-derived M phi respond to LPS by tumor necrosis factor-alpha release and procoagulant activity upregulation by a similar dose response curve in the presence or absence of serum, suggesting that humoral factors such as LBP are relatively unimportant in the activation of M phi. Both serum-dependent and serum-independent activation of M phi by LPS require cellular CD14, as evidence by blocking studies with CD14-specific antibodies. Clones from the monocytoid cell line Mono Mac-6 selected for high LPS sensitivity displayed similar properties. When washed free of serum and cultured in the presence of calcitriol, they responded to LPS in a similar manner, regardless of the presence or absence of serum, and this response was inhibited by anti-CD14. It is hypothesized that during their differentiation. M phi acquire a functional substitute for the serum factor LBP, thereby being able to recognize low LPS concentrations in a milieu low in LBP concentration. It will be of interest to determine whether this is a high-affinity LBP receptor, LBP itself, or another cell surface constituent.
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PMID:Human macrophages respond to LPS in a serum-independent, CD14-dependent manner. 903 Sep 80

In order to further elucidate effect of hemorrhagic shock on endotoxin-inducing cytokine production, the present study was designed to investigate the production of tumor necrosis factor alpha (TNF alpha) induced by low-dose (1 microgram/kg) of lipopolysaccharide (LPS) and its cellular sources after hemorrhagic shock (HS) in rats. With combination of expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs, and kidneys, we further analyzed a possible mechanism for increasing sensitivity to LPS by shock. We found in vivo that plasma TNF alpha levels in the HS + LPS group were 20-fold higher than those in the HS group (p < .01) and 2.7-fold higher than those in the LPS group (p < .05). It was shown in vitro that the capacity of the peripheral white blood cells to produce TNF alpha in response to LPS stimulation was significantly decreased by 126% (p < .01) and 57% (p < .05) compared with the pre-shock levels and sham group, respectively, at the end of resuscitation following shock, and still markedly inhibited 3 h after resuscitation, while the capacity of hepatic Kupffer's cells to produce TNF alpha was significantly increased by 110% compared with the sham group (p < .01) after shock and resuscitation. Results from RT-PCR showed that expression of LBP mRNA in the liver, lungs, and kidneys was increased after shock and resuscitation. It is suggested that hemorrhagic shock could significantly strengthen endotoxin to induce TNF alpha production, which might be due to up-regulation of LBP expression in tissues after shock, and the tissue macrophage population may be the main source for cytokine production in shock.
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PMID:Effect of hemorrhagic shock on endotoxin-inducing TNF production and intra-tissue lipopolysaccharide-binding protein mRNA expression and their relationship. 906 87

The interaction of lipopolysaccharide binding protein (LBP) with apolipoprotein (apo)A-I on high density lipoproteins (HDL) was studied in solid phase ligand binding assays with a biotinylated LBP-specific antibody. The association was dependent on LBP concentration and enhanced in the presence of lipopolysaccharide (LPS). Maximal enhancement was measured at an LPS/LBP molar ratio of 6. To identify regions on apoA-I that participate directly or indirectly in the interaction between LBP and HDL, we attempted to inhibit LBP association with a panel of mapped apoA-I-specific monoclonal antibodies. Whereas some antibodies were effective inhibitors, others were not, even though they bound apoA-I. Furthermore, selected apoA-I synthetic peptides inhibited the antibody-mediated interference of the HDL/LBP interaction. Although no specific mechanism can be defined for the basis of the inhibitory effects of the antibodies on the association of LBP with HDL, we identified a role for three unique regions on apoA-I between residues 1-31, 95-164, and 178-200. These results suggested that apoA-I is a key component in the association of LBP with HDL and may play an important role in the biologic activity of LPS/LBP complexes.
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PMID:Structural determinants for the interaction of lipopolysaccharide binding protein with purified high density lipoproteins: role of apolipoprotein A-I. 910 32

The effects of bacterial endotoxin (lipopolysaccharide, LPS) are amplified by lipopolysaccharide binding protein (LBP) and CD14, resulting in cellular activation at very low concentrations of LPS. To investigate the importance of this pathway in acute lung injury, we measured LPS, LBP, and soluble CD14 (sCD14) in the bronchoalveolar lavage fluid (BAL) of 82 patients with acute respiratory distress syndrome (ARDS). LBP and sCD14 increased markedly in BAL of patients with ARDS. sCD14 and LBP each were strongly related to BAL total protein and polymorphonuclear neutrophil (PMN) concentration, whereas LPS concentration was not. Multivariate analyses showed sCD14 to be strongly related to BAL total protein, even after controlling for LPS and LBP concentrations. sCD14 was strongly and independently related to PMN concentration, after controlling for BAL LPS, LBP, and interleukin-8 (IL-8). The BAL LPS concentration was not strongly related to either BAL total protein or BAL PMN. The BAL sCD14 and LBP values were similar in all subgroups of patients with ARDS, and were not related to survival. The serum LBP and sCD14 were elevated in ARDS, but were not related to BAL total protein, LBP, sCD14, PMN, or clinical outcome. Thus, LBP and sCD14 reach high concentrations in the lungs of patients with ARDS, and BAL sCD14 is strongly related to two major indices of lung inflammation: total protein and PMN concentration. CD14-dependent mechanisms may contribute to lung inflammation in ARDS.
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PMID:Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome. 911 29

To determine the role of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-induced inflammation, 12 healthy subjects received an intravenous injection with LPS (2 ng/kg) preceded by infusion of either a recombinant human dimeric TNF receptor type II-IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) or vehicle (n = 6) from -30 minutes to directly before LPS injection. LPS elicited a transient increase in plasma TNF activity, peaking after 1.5 hours (219 +/- 42 pg/mL; P < .05). Infusion of TNFR:Fc completely neutralized endogenous TNF activity. LPS administration was associated with an early activation of fibrinolysis (plasma concentrations of tissue-type plasminogen activator, plasminogen activator activity, and plasmin-alpha2-antiplasmin complexes), followed by inhibition (plasma plasminogen activator inhibitor type I), changes that were completely prevented by TNFR:Fc. By contrast, TNFR:Fc did not influence LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2 and thrombin-antithrombin III complexes). TNFR:Fc strongly inhibited endothelial cell activation (plasma levels of soluble E-selectin), modestly reduced neutrophil responses (neutrophilia and plasma concentrations of elastase-alpha1-antitrypsin complexes and lactoferrin), but did not affect the release of secretory phospholipase A2 or lipopolysaccharide-binding protein (P > .05). Infusion of TNFR:Fc only (without LPS) in another 6 normal subjects did not induce any inflammatory response. These data indicate that TNF is involved in only some inflammatory responses to intravenous LPS in humans.
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PMID:Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans. 916 Jun 78

An invading pathogen must be held in check by the innate immune system until a specific immune response can be mounted. In the case of Gram-negative bacteria, the principal stimulator of the innate immune system is lipopolysaccharide (LPS), a component of the bacterial outer membrane. In vitro, LPS is bound by lipopolysaccharide-binding protein (LBP) and transferred to CD14--the LPS receptor on the macrophage surface--or to high-density lipoprotein (HDL) particles. Transfer to CD14 triggers an inflammatory response which is crucial for keeping an infection under control. Here we investigate how LBP functions in vivo by using LBP-deficient mice. Surprisingly, we find that LBP is not required in vivo for the clearance of LPS from the circulation, but is essential for the rapid induction of an inflammatory response by small amounts of LPS or Gram-negative bacteria and for survival of an intraperitoneal Salmonella infection.
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PMID:Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. 933 87


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