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

Endotoxins, the lipopolysaccharide (LPS) moieties on the bacterial cell wall, cause many of the pathological features of Gram-negative septicemia. Tumor necrosis factor (TNF), primarily a product of monocyte/macrophages, has been shown to mediate many of the pathophysiological effects of endotoxin. Kupffer cells, the largest macrophage population in the body, release TNF when stimulated by LPS in vitro. A recombinant human hybrid interferon-alpha A/D (rIFN-alpha) markedly inhibited this LPS-elicited TNF production by Kupffer cells. The effects of rIFN-alpha were further tested in C57BL/6 mice receiving a lethal dose (400 micrograms/mouse) of LPS. All LPS-treated mice died within 2 days. Pretreatment with rIFN-alpha 1 h before LPS challenge improved the survival at 3 days to 22% (5/23, p < 0.04). In contrast, rIFN-alpha was more effective when administered 20 min after LPS injection, increasing the survival rate to 81% (13/16, p < 0.0001). TNF mRNA expression in the liver and spleen 50 min after LPS challenge, and plasma TNF 1.5 h after LPS were also reduced by either pretreatment or post-treatment with rIFN-alpha. Subsequently, experiments were carried out to test the efficacy of delayed rIFN-alpha treatment. A significant protective effect was still apparent when rIFN-alpha was administered 6, 10 and even 14 h (81%, 62% and 28% survival, respectively) after LPS challenge when serum TNF levels had already returned to near baseline. These experimental results suggest that rIFN-alpha might have a therapeutic potential for the prevention and treatment of the deleterious effects associated with endotoxemia besides mechanisms initially blocking TNF production.
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PMID:Interferon-alpha prevents endotoxin-induced mortality in mice. 144 3

Gram-negative septicemia remains one of the most serious forms of hospital-acquired infection. The most consistently virulent component of the gram-negative lipopolysaccharide (endotoxin) appears to be lipid A. Elucidation of the structure-function relationships of lipid A and the biochemical configurations required for endotoxicity makes possible the design of lipopolysaccharide antagonists and/or the production of poly- or monoclonal antibodies that may abrogate the biologic effects of endotoxin. The mechanisms of activity of lipopolysaccharide and the pathophysiologic events it triggers are now better understood than in the recent past. Lipid A triggers the release of mediators such as cachectin (tumor necrosis factor), thereby initiating a cascade of potentially lethal events. Although recent studies indicate no routine role for corticosteroids in gram-negative septic shock or acute respiratory distress syndrome, considerable progress has been made in the development of effective antibiotics. Recent studies of septicemia in neutropenic patients show survival rates significantly higher than those reported more than two decades ago.
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PMID:University of California/Davis Interdepartmental Conference on gram-negative septicemia. 168 79

Gram negative sepsis/septic shock continues to be a major cause of morbidity and mortality in newborns. We studied the effects of anti-inflammatory drugs, indomethacin (IND) and dexamethasone (DX), on glucoregulation, body weight, and mortality in 10-day-old suckling rats administered Salmonella enteritidis lipopolysaccharide (LPS). IND (1.5 mg/kg) or DX (4 mg/kg) was intraperitoneally (ip) administered immediately after highly lethal LPS injection. Both IND and DX attenuated the LPS-induced hypoglycemia and lactacidemia, and decreased the mortality, IND did not alter body weight changes in rats with septic shock. DX continued a catabolic state and reduced their body weights. In rats fasted for 24 hr before LPS injection, DX, but not IND, increased the mortality. We concluded that IND and DX improved the LPS-induced glucose dyshomeostasis and decreased the mortality of endotoxic shock in 4-hr-fasted 10-day-old rats. Per contra, DX was detrimental in 24-hr-fasted 10-day-old endotoxic rats.
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PMID:Dexamethasone and indomethacin treatment during endotoxicosis in the suckling rat. 225 15

Serum antibody to lipopolysaccharide core glycolipid was measured in normal children and in full term and premature (less than or equal to 1500 g) infants. Antilipopolysaccharide core glycolipid antibody was present in term infants and normal children, and reached adult titres by 15 years of age. The specific anti core glycolipid antibody was predominately of the IgG class. Preterm infants (less than 32 weeks' gestation) had significantly lower titres of antilipopolysaccharide core glycolipid than more mature preterm or term infants. The results suggest that administration of anticore glycolipid immunoglobulin may be beneficial in the treatment or prevention of Gram negative septicaemia in preterm and very young infants.
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PMID:Serum immunoglobulins to endotoxin core glycolipid: establishment of normal concentrations. 227 Sep 49

Lipopolysaccharide affects a variety of eukaryotic cells and mammalian organisms. These actions are involved in the pathogenesis of Gram-negative septicemia. Many of the actions of lipopolysaccharide are believed to be caused by its active moiety, lipid A. Our laboratory has previously identified a bioactive lipid A precursor, termed lipid IVA (Raetz, C. R. H., Purcell, S., Meyer, M. V., Qureshi, N., and Takayama, K. (1985) J. Biol. Chem. 260, 16080-16888), which can be labeled with 32P of high specific activity and purified. In this work we have used the labeled probe, 4'-32P-lipid IVA, to develop a novel assay for the specific binding of lipid IVA to whole cells. We have also demonstrated its use in a ligand blotting assay of immobilized cellular proteins. Using the whole cell assay, we show that 4'-32P-lipid IVA specifically binds to RAW 264.7 macrophage-like cultured cells. The binding is saturable, is inhibited with excess unlabeled lipid IVA, and is proteinase K-sensitive. It displays cellular and pharmacological specificity. Using the ligand blotting assay, we show that several RAW 264.7 cell proteins can bind 4'-32P-lipid IVA. The two principal binding proteins have Mr values of 31 and 95 kDa, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Fractionation studies indicate that the 31-kDa protein is enriched in the nuclear fraction and may be a histone, whereas the 95-kDa protein is enriched in the membrane fraction. The binding assays that we have developed should lead to a clearer understanding of lipid A/animal cell interactions.
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PMID:Lipid A binding sites in membranes of macrophage tumor cells. 317 May 65

Human monoclonal IgM antibody HA-1A, which recognizes the lipid A component of bacterial lipopolysaccharide (LPS), has been shown to reduce mortality in Gram negative septicemia. The vascular endothelial lining of blood vessels, which controls leucocyte traffic and activation, as well as haemostatic balance, may be one of the primary targets of LPS action during sepsis. In earlier studies we have described HA-1A-induced immune adherence of LPS to complement receptors on erythrocytes, and showed that pre-incubation with HA-1A, in the presence of complement and red blood cells, markedly reduced LPS-induced cytokine production from peripheral blood mononuclear cells. In the present study, we measured the effect of immune adherence of LPS in the presence of HA-1A on the responses of cultured endothelial cells, and found that subsequent expression of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and secretion of the cytokines interleukin-6 and granulocyte-macrophage colony stimulating factor were markedly reduced. Moreover, the ability of LPS to increase levels of tissue factor procoagulant activity on endothelial cells was markedly diminished by LPS immune adherence to HA-1A. This decrease in endothelial activation in response to LPS following immune adherence to HA-1A may play a significant role in the protective effect of HA-1A in vivo during the course of Gram negative sepsis.
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PMID:Antilipid A monoclonal antibody HA-1A decreases the capacity of bacterial lipopolysaccharide to activate human vascular endothelial cells by an immune adherence mechanism. 751 52

Cardiovascular collapse associated with Gram-negative septicemia is believed to result from the stimulation of phagocytes by bacterial lipopolysaccharide (endotoxin, LPS). It remains unclear how endotoxin activates phagocytes, but recent evidence suggests the involvement of the glycosyl phosphatidylinositol-linked myelocyte antigen, CD14. We report that transfection of human CD14 into Chinese hamster ovary fibroblasts transfers macrophage-like responsiveness to otherwise LPS-unresponsive cells. These data demonstrate that LPS-induced responsiveness can be transferred to a heterologous non-responder cell type by expression of a single leukocyte-specific gene product.
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PMID:Surface expression of human CD14 in Chinese hamster ovary fibroblasts imparts macrophage-like responsiveness to bacterial endotoxin. 769 22

The presence of endotoxin from Gram-negative bacteria signals the innate immune system to up-regulate bacterial clearance and/or killing mechanisms. Paradoxically, such responses also contribute to septic shock, a clinical problem occurring with high frequency in Gram-negative septicemia. CD14 is a receptor for endotoxin (lipopolysaccharide, LPS) and is thought to have an essential role in innate immune responses to infection and thereby in the development of septic shock. Using a novel rabbit model of endotoxic shock produced by multiple exposures to endotoxin, we show that anti-rabbit CD14 mAb, which blocks LPS-CD14 binding, protects against organ injury and death even when the antibody is administered after initial exposures to LPS. In contrast, anti-rabbit tumor necrosis factor mAb treatment fails to protect when administered after LPS injections. These results support the concept that anti-CD14 treatment provides a new therapeutic window for the prevention of pathophysiologic changes that result from cumulative exposures to LPS during septic shock in man.
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PMID:Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin. 981 94

Gram negative sepsis and septic shock continue to be a major medical problem, with a complex physiopathology and it is associated with high mortality. Although secretion of cytokines such as tumor necrosis factor-alpha by macrophages is the principal host mediator of septic shock, other characteristic functions of macrophages implicated in their phagocytic capacity have not been studied in the process of endotoxic shock. In the present study we have used an intraperitoneal injection of E. coli lipopolysaccharide (LPS) (100 mg/kg) in order to obtain an endotoxic shock model in adult female BALB/c mice. Peritoneal cell suspensions were obtained at several times (2, 4, 12 or 24 h) after injection and the following functions were studied on the peritoneal macrophages: adherence to substrate, mobility (spontaneous and directed or chemotaxis), ingestion of particles and superoxide anion production. The results showed a stimulation of adherence, ingestion and superoxide production as well as a decrease of chemotaxis in the animals injected with LPS. These effects changed with time after LPS injection. Thus, the increase of adherence and the decrease of mobility were higher during the first hours, whereas the increase in ingestion and superoxide production turned larger with time.
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PMID:Effects of endotoxic shock in several functions of murine peritoneal macrophages. 987 50

Previously, it was reported that A(1) adenosine receptor antagonists prevent endotoxin-induced acute lung injury and pulmonary arterial endothelial cell damage. In competition radioligand binding experiments in membranes prepared from human pulmonary artery endothelial cells (PAECs), lipopolysaccharides (LPSs) of Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas aeruginosa displaced the binding of a selective A(1) adenosine receptor antagonist [(125)I]-BWA844U (IC(50) values: 195 ng/ml, 290 ng/ml, 602 ng/ml, and 693 ng/ml, respectively) in a dose-dependent, competitive manner. There was no displacement of this radioligand by enterotoxin (< or = 10 microg/ml), diphosphoryl lipid A (< or = 10 microg/ml), and glycolipids, monosialoganglioside (< or = 1 microg/ml), lactocerebroside (< or = 100 microg/ml), or NBD galactocerebroside (< or = 100 microg/ml). Based on calculated IC(50) values, LPS (E. coli, IC(50) 111 ng/ml) displaced the selective A(1) adenosine receptor agonist, [(3)H]-2-chloro, N(6)-cyclopentyladenosine (CCPA) in human PAECs with a potency profile, CCPA > LPS > 2-phenylaminoadenosine (CV 1808), a selective A(2) adenosine receptor agonist. The potency profile for displacement of the selective A(2a) adenosine receptor agonist [(3)H]-CGS 21680 was CV 1808 > CCPA. LPS (E. coli 0.1 pg/ml-10 microg/ml) did not displace [(3)H]-CGS 21680 binding. In human PAECs, IL-6 and TXA(2) release induced by LPS (0-1 microg/ml) or CCPA (0-1 microM) at high doses was significantly reduced by the selective A(1) adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1 microM). These data suggest that LPS binds to and activates A(1) adenosine receptors on human PAECs to induce the release of IL-6 and TXA(2). Activation of A(1) adenosine receptors on human PAECs by LPS, may contribute to the pathophysiology of acute lung injury associated with Gram-negative septicemia and endotoxemia.
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PMID:Lipopolysaccharide binds to and activates A(1) adenosine receptors on human pulmonary artery endothelial cells. 1223 Sep 16


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