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

The unexplained occurrence of thrombocytopenia in cases of Gramnegative sepsis in man led us, in the light of animal experiments indicating the blood platelet as the target cell for endotoxin, to examine the effect of Salmonella enteritidis lipopolysaccharide B on human platelets. Human platelets were separated from a coat of plasma proteins by Sepharose 2B filtration or by a combined procedure of albumin gradient and Sepharose 2B filtration. The action of endotoxin on human platelets resulted in membrane changes manifested by dose-dependent release of [3H]serotonin and adenine nucleotides. Cytoplasmic marker, lactic dehydrogenase, and lysosomal marker, beta glucuronidase, were retained indicating that the release reaction was selective. Release of [3H]serotonin was specific for endotoxin since other particulates, zymosan and erythrocyte stroma, were without effect. Endotoxin, added to gel-filtered human platelets, induced a significant evolution of platelet factor 3 procoagulant activity. Preincubation of endotoxin with a membrane-rich homogenate of human platelets inhibited its labilizing effect on human platelets thus suggesting an interaction between endotoxin and the platelet membrane itself. Other plausible factors in this interaction [fibrinogen, adenine nucleotides, thrombin, sialic acid residues, and IgG] were eliminated on the basis of a series of control experiments. From the negligible effect of aspirin and indomethacin, we may infer that the interaction of endotoxin with platelets does not depend on the platelet prostaglandin synthesis pathway. The direct interaction of endotoxin with the human platelet membrane comprises a new mechanism which may help to clarify the pathogenesis of vascular and haemostatic disorders accompanying bloodstream infections due to Gram-negative bacteria.
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PMID:Membrane changes in human platelets induced by lipopolysaccharide endotoxin. 32 97

Injection of bacterial lipopolysaccharide into pregnant mice resulted in fibrinogen accumulation, thrombosis and haemorrhage in the placental tissue and foetal death. Depletion of circulating fibrinogen by a thrombin-like enzyme from the venom of Malayan pit viper, Arvin, prevents foetal death. Foetal protection was also obtained by treating the mothers with a preparation of phospholipase C from Bacillus cereus known to inactivate tissue thromboplastin. It is suggested the lipopolysaccharide causes foetal death by inducing thrombosis as a consequence of activation of placental thromboplastin.
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PMID:Protection of pregnant mice with phospholipase C and with Arvin against foetal death induced by bacterial lipopolysaccharide. 44 21

Sublethal doses of vincristine (VNC) and bacterial lipopolysaccharide (LPS) administered simultaneously to adult male mice resulted in markedly enhanced mortality. All of 10 strains of Pseudomonas aeruginosa tested, 4 of 7 strains of Bacteroides, and 6 of 10 strains of Listeria monocytogenes were able to substitute for purified LPS in enhancing mortality in VNC-treated mice. Inoculation of mice with each of 10 strains of Pseudomonas, each of 7 strains of Bacteroides, and about half of the 10 strains of Listeria tested elicited increased resistance to the lethal action of purified LPS. The patterns of responses of mice receiving a lethal combination of 2 mg of LPS/kg and 1 mg of VNC/kg resembled those of mice receiving a lethal dose of 10 mg of VNC/kg alone or 15 mg of LPS/kg alone with respect to (i) serum glutamic pyruvate transaminase activity, (ii) hematocrit values, and (iii) thrombocytopenia. The patterns of responses of mice receiving a lethal combination of LPS and VNC resembled those of mice receiving a lethal dose of LPS alone with respect to (i) hypothermia, (ii) retention of sulfobromophthalein, (iii) fibrinogen level, (iv) prothrombin activity, (v) blood urea nitrogen levels, and (vi) time of death. These data are consistent with the proposition that the combination of VNC and LPS produces a fatal renal failure. Histological studies confirmed that there was extensive renal damage in mice treated with lethal doses of LPS alone or a lethal combination of LPS and VNC.
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PMID:Enhanced toxicity for mice of combinations of bacterial lipopolysaccharide and vincristine. 94 80

Changes in the plasma thrombomodulin (TM) level were examined in endotoxin-infused rabbits. The plasma TM level in normal rabbits was 143.8 +/- 8.4 ng/ml (n = 67) and the molecular weight of the major TM was about 55 kd. Endotoxin (lipopolysaccharide, LPS, E. Coli B8:0127) was intravenously infused. LPS infusion increased the plasma TM level dose-dependently between 0.2 mg/kg and 5 mg/kg. When 5 mg/kg LPS was infused, the plasma TM level started to increase immediately and was 2.3 times higher than the control value within 1 hr. The molecular weight of the major TM was about 75 kd. This rapid increase in TM occurred before the decrease in fibrinogen content and the prolongation of prothrombin time. To examine the effect of circulating leukocytes on the TM increase in endotoxin-infused rabbits, 5 mg/kg LPS was infused into rabbits with leukocytopenia induced by X-ray irradiation. The maximum plasma level of TM was significantly lower than in the untreated rabbits given LPS. These data suggest that the increase in plasma TM is caused by LPS-stimulated leukocyte's prior to hemostaseological changes. It is well known that endothelial cells can be injured by stimulated leukocytes, so this increase in plasma TM probably reflects the deterioration of endothelial cells. This deterioration decreases the ability of endothelial cells to inhibit thrombosis, which would, in turn, contribute to the development of disseminated intravascular coagulation in endotoxin-infused rabbits.
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PMID:Changes in thrombomodulin level in plasma of endotoxin-infused rabbits. 131 90

Thrombomodulin (TM) is an endothelium-associated glycoprotein that converts thrombin from a procoagulant protease to an anticoagulant. Thrombin, a key enzyme in thrombus formation, binds to TM molecules on endothelium with very high affinity. After binding to TM, thrombin fails to act on the coagulation factors and platelets, and its ability to activate protein C is enhanced more than 1000-fold. We expressed soluble recombinant TM (rTM) in CHO cells and evaluated its antithrombotic effect on thrombin-induced thromboembolism in mice and lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats. Thrombin injection into mouse caused acute thromboembolism resulting instantaneous death, however preinjection of rTM neutralized the lethal effect of thrombin in a dose-dependent manner. Soluble rTM also improved the consumption of fibrinogen and platelets in experimental DIC-rats induced by LPS. The effect of rTM was confirmed in histologically. These data suggest that rTM may have a therapeutic effect on thrombosis or DIC in human.
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PMID:[Therapeutic evaluation of recombinant thrombomodulin]. 133 21

The adhesive interactions of circulating blood cells are tightly regulated, receptor-mediated events. To establish a model for studies on regulation of cell adhesion, we have examined the adhesive properties of the HD11 chick myeloblast cell line. Function-perturbing antibodies were used to show that integrins containing the beta 1 subunit mediate HD11 cell attachment to several distinct extracellular matrix proteins, specifically fibronectin, collagen, vitronectin, and fibrinogen. This is the first evidence that an integrin heterodimer in the beta 1 family functions as a receptor for fibrinogen. While the alpha v beta 1 heterodimer has been shown to function as a vitronectin receptor on some cells, this heterodimer could not be detected on HD11 cells. Instead, results suggest that the beta 1 subunit associates with different, unidentified alpha subunit(s) to form receptors for vitronectin and fibrinogen. Results using function-blocking antibodies also demonstrate that on these cells, additional receptors for vitronectin are formed by alpha v beta 3 and alpha v associated with an unidentified 100-kD beta subunit. The adhesive interactions of HD11 cells with these extracellular matrix ligands were shown to be regulated by lipopolysaccharide treatment, making the HD11 cell line attractive for studies of mechanisms regulating cell adhesion. In contrast to primary macrophage which rapidly exhibit enhanced adhesion to laminin and collagen upon activation, activated HD11 cells exhibited reduced adhesion to most extracellular matrix constituents.
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PMID:Adhesion of a chicken myeloblast cell line to fibrinogen and vitronectin through a beta 1-class integrin. 137 May

In a rhesus monkey endotoxin sepsis model established by intravenous administration of 300 mg/kg D-galactosamine and 0.1 microgram/kg lipopolysaccharide from Salmonella abortus equi, hemodynamic, respiratory, metabolic and hematologic variables; levels of blood gases; monkey leukocyte elastase levels, and blood plasma concentrations of tumor necrosis factor--alpha (TNF) were monitored for 6 hours after administration, and again after 24 hours. Thirty minutes after administration of lipopolysaccharide, either 15 mg/kg anti-TNF monoclonal antibody (MoAB; n = 6) or vehicle placebo (saline solution; n = 4) were given intravenously. During this short-term experiment the organ functions were not different between the treatment groups. However, anti-TNF MoAb afforded morphologic protection from heart, lung, liver, and kidney damage after lipopolysaccharide challenge. Coagulation responses (platelet count and levels of fibrinogen, antithrombin III, and thrombin-antithrombin III complex) were smaller in anti-TNF MoAB-treated monkeys. Plasma TNF levels (WEHI cell cytotoxicity assay) reached a peak (350 pg/ml) 60 minutes after lipopolysaccharide administration in vehicle control subjects but no TNF was detected in the anti-TNF MoAB-treated monkeys. All control animals died 67 +/- 30 hours after lipopolysaccharide administration from multiorgan failure. On the contrary, all anti-TNF MoAB-treated animals survived 14 days (p > 0.005 vs placebo group mortality). Thus in short-term monkey experiments our study indicates protection against lipopolysaccharide-induced endotoxin sepsis by anti-TNF MoAB, which may have clinical relevance for the treatment of human septicemia.
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PMID:Monoclonal antibody to tumor necrosis factor--alpha prevents lethal endotoxin sepsis in adult rhesus monkeys. 140 33

We have evaluated the effect of 1-Deamino-8D-arginine vasopressin (DDAVP) on an experimental model of intravascular coagulation (DIC) induced in rabbits by injection of 20 micrograms kg-1 h-1 during 6 h of E. coli lipopolysaccharide. DDAVP significantly ameliorated the platelet drop and fibrinogen decrease (p less than 0.01) induced by endotoxin in control animals. A significant reduction in factor XII consumption (p less than 0.01) and a decrease in the generation of endotoxin induced PAI-1 activity in rabbits circulation was also observed (p less than 0.005). Moreover, fibrin deposition in kidneys of rabbits receiving DDAVP was significantly reduced as compared to control animals. Finally, the mortality rate in the control group was significantly higher than in DDAVP-treated rabbits (p less than 0.01). The hemostatic changes induced by DDAVP correlated with lower fibrin deposition and reduction in mortality rates.
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PMID:Effect of DDAVP on endotoxin-induced intravascular coagulation in rabbits. 144 Apr 97

Endotoxin, a lipopolysaccharide (LPS), is a bacterial cell wall product instrumental in producing deleterious host responses to infection. This LPS appears to act, in part, by triggering release of endogenous mediators such as cytokines. Repeated exposures to endotoxin produce attenuated responses to this molecule. To examine the mechanisms and biologic consequences of this tolerance to LPS, Wistar rats were subjected to a 14-day course of LPS administration. Tolerance to LPS with regard to anorexia, weight loss, and acute-phase responses was noted. Attenuation of these physiologic responses was accompanied by abrogation of circulating cytokine appearance in response to endotoxin, suggesting that tolerance to LPS is in part due to a decreased production of cytokines. Tolerance to LPS also diminished the response to a subsequent infected thermal injury, as measured by food intake, body weight, fibrinogen levels, and mortality. Thus, clinical conditions involving repeated exposure to LPS may modify the host's responses to subsequent injury. The attenuated responses to injury accompanying the decreased production of cytokines further implicate cytokines in the pathogenesis of injury and disease.
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PMID:Tolerance to endotoxin prevents mortality in infected thermal injury: association with attenuated cytokine responses. 156 35

It has been postulated that Kupffer cells provide signals that regulate hepatocyte responses in sepsis and inflammation. Although in vitro data support such a hypothesis, to our knowledge, no in vivo evidence has been reported. We injected rats with lipopolysaccharide intraperitoneally to simulate sepsis or turpentine intramuscularly to mimic localized inflammation. Both treatments are known to induce the hepatic acute-phase response. Liver nonparenchymal cells and hepatocytes were isolated and placed in culture. Hepatocyte fibrinogen synthesis was measured as an indication of interleukin 6 exposure, while nonparenchymal interleukin 6 production was measured directly. Both lipopolysaccharide and turpentine stimulated a sharp increase in hepatocyte fibrinogen synthesis (turpentine greater than lipopolysaccharide). However, only lipopolysaccharide injection was associated with increased nonparenchymal cell interleukin 6 synthesis. Increased circulating levels of interleukin 6 could be found only after lipopolysaccharide injection. In addition, tumor necrosis factor synthesis was enhanced by lipopolysaccharide but not turpentine. Our data show that nonparenchymal cells are stimulated to provide the interleukin 6 signal to hepatocytes in endotoxemia but not in remote localized inflammation, even though both treatments stimulate the hepatic acute-phase response. Our findings support paracrine functions for liver sinusoidal cells in certain septic states.
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PMID:Liver nonparenchymal cells are stimulated to provide interleukin 6 for induction of the hepatic acute-phase response in endotoxemia but not in remote localized inflammation. 173 48


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