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

We have discovered that the immune system processes proopiomelanocortin (POMC) products differently depending on the stimulus for induction. We have shown that corticotropin-releasing factor (CRF) induces the lymphocytes from C3HeB/FeJ lipopolysaccharide (LPS)-sensitive mice to produce adrenocorticotropin (ACTH) 1-39 and beta-endorphin, whereas LPS induces these lymphocytes to produce ACTH 1-23 to 26 and alpha- or gamma-endorphin. We have proposed that the smaller species of ACTH and endorphin are proteolytic cleavage products from ACTH 1-39 and beta-endorphin. Analysis of C3HeB/FeJ LPS-treatment B lymphocyte lysates showed an enzymatic activity at pH 5 but not pH 7 that cleaved ACTH 1-39 into a smaller ACTH 1-23 to 26. The B lymphocytes from C3H/HeJ (LPS-resistant) mice expressed but did not process proopiomelanocortin after LPS or CRF treatment, nor did their B cells express the aforementioned enzymatic activity. Taken together, these data suggest a unique processing pathway in LPS-treated B lymphocytes and one in which immunoreactive (ir)-endorphins may play a role in the pathophysiology of endotoxic shock.
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PMID:Novel processing pathway for proopiomelanocortin in lymphocytes: endotoxin induction of a new prohormone-cleaving enzyme. 282 3

Lipid A is the toxic principle of lipopolysaccharide of gram-negative bacteria, which causes a spectrum of changes in blood cells and vascular cells. We now report that human platelets are directly stimulated by endotoxic lipid A that activates protein kinase C. Rapid phosphorylation of a human platelet protein of Mr 47,000, a marker of protein kinase C activation, accompanies secretion of [14C]serotonin and aggregation triggered by endotoxic lipid A. These events are time and concentration dependent, with phosphorylation reaching maximum in 2 min and the concentration of lipid A causing a 50% effect (EC50) between 12 and 15 microM. Phospholipase C activation in lipid A-stimulated platelets was not observed as judged by a lack of generation of [3H]diacylglycerol in [3H]arachidonic acid-labeled platelets and a lack of generation of [32P]-phosphatidic acid in 32PO4-labeled platelets. Lipid A did not induce formation of TXA2 as measured by radioimmunoassay for TXB2. The stimulation of human platelets and activation of protein kinase C by endotoxic lipid A was blocked by lipid X, a structural precursor of lipid A. Lipid X also blocked the stimulation of human platelets by phorbol 12-myristate 13-acetate, suggesting that lipid A, lipid X and phorbol ester share reactive site(s) on the human platelet membrane. Although lipid X inhibited thrombin-induced phosphorylation of P47 it did not suppress secretion of [14C]serotonin, indicating the role of protein kinase C-independent pathways in platelet stimulation by thrombin. The inhibitory effect of lipid X did not involve generation of cyclic AMP in human platelet membrane preparations. These results indicate that human platelets are stimulated by endotoxic lipid A, a naturally occurring biologic modifier of protein kinase C. Due to the widespread presence of this enzyme in blood cells, vascular cells, and neurons, its modulation by lipid A may represent a significant mechanism underlying hematologic and circulatory derangements observed in endotoxic shock in humans.
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PMID:Modulation of human platelet protein kinase C by endotoxic lipid A. 304 71

Lipopolysaccharides (LPS) from Gram-negative bacteria are considered to be the responsible agents for the induction of endotoxic shock, affecting the liver as a target organ. In this study, the cell morphology and some biochemical properties of 24 h-culture-hepatocyte monolayers treated with Escherichia coli 0111:B4 lipopolysaccharide, were observed. Cell morphology was observed by scanning electron microscopy and immunofluorescence methods. LPS interaction induced an increase in rounded cells with diminished adhesion capacity. As biochemical parameters, albumin synthesis and 2-deoxyglucose uptake were measured. LPS decreased the hexose uptake in a dose-dependent manner. Binding of (14C)LPS to cultured hepatocytes showed that LPS binds to non-specific constituents of the membrane bilayer.
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PMID:Morphological damage induced by Escherichia coli lipopolysaccharide in cultured hepatocytes: localization and binding properties. 305 62

Antiserum to Escherichia coli J5, a mutant endotoxin (LPS) which contains only core determinants, has proven effective in reducing mortality from endotoxic shock due to a wide variety of gram-negative bacteria. Twenty New Zealand white rabbits with coliforms in the gut were subjected to hemorrhagic shock of 36 mm Hg for 3 hr. Treated rabbits were resuscitated with 15 cc of rabbit J5 antiserum (hemagglutinating antibody titer against J5 lipopolysaccharide of 1:1024), remaining shed blood, and lactated Ringer's to achieve a mean arterial blood pressure (MABP) within 20% of baseline. The control group was similarly resuscitated but received 15 cc normal rabbit serum (titer 1:2). Catheters were removed and rabbits were returned to their cages until death or 5 days of survival. Hemodynamic parameters (heart rate, MABP, cardiac output, and total peripheral resistance) did not differ significantly between groups. However, six treated rabbits survived 5 days (60%) and no control rabbit lived past the third postexperimental day (P less than 0.019). Our data suggest that systemic endotoxemia may contribute to morbidity and mortality in severe hemorrhagic shock.
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PMID:Antiserum to endotoxin in hemorrhagic shock. 305 23

Reversible endotoxic shock was induced in adult rats by i.v. injection of Escherichia coli O111:B4 lipopolysaccharide (1.6 mg/100 g). The shock progression was evaluated by measuring serum glucose levels as well as activities of aspartate aminotransferase (GOT) and alkaline phosphatase in serum. A rapid increase of serum glucose levels occurs, after LPS injection, followed by hypoglycaemia (minimum values at 6 h) with progressive reversion to control values. Serum GOT activity increased (twofold) 6 h after endotoxin administration and returned to control values at 72 h. No appreciable changes occurred in serum alkaline phosphatase activity. Endotoxaemia produced a decrease in the cytochrome P-450 levels in all target organs considered: lung, adrenal glands and liver. The progressive decrease in the serum albumin concentration as well as changes of the physical properties of the plasma membranes observed in vivo, can not be explained only by direct interaction of endotoxin with the target organs, underlining the importance of serum mediators in the induction of the shock response.
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PMID:Induction of reversible shock by Escherichia coli lipopolysaccharide in rats. Changes in serum and cell membrane parameters. 306

Lipid A analyses confirm not only the present taxa of the purple nonsulfur bacteria (formerly Rhodospirillaceae), but also phylogenetical relatedness of distinct phototrophic to distinct non-phototrophic bacteria, as was suggested by cataloguing 16S rRNA. For example, lipid A with ester-bound 3-OH-10:0 and the rare amide-linked 3-oxo-14:0 is common to the phototrophic Rhodobacter capsulatus and Rhodobacter sphaeroides and also to Paracoccus denitrificans and Thiobacillus versutus. 'Lipid ADAG' (lipid A with 2,3-diamino-D-glucose (DAG)) occurs in the phototrophic Rhodopseudomonas viridis and Rhodopseudomonas palustris and also in the related non-phototrophic species, e.g., Nitrobacter winogradskyi, Pseudomonas diminuta, or Thiobacillus ferrooxidans. The phylogenetically more coherent purple sulfur bacteria (Chromatiaceae) uniformly contain D-mannose in their phosphate-free lipid A. Among the green bacteria, only the Chlorobiaceae but not the likewise chlorosome-containing Chloroflexaceae contain lipopolysaccharide. Lipid ADAG from R. viridis is a structural analogue of a biosynthetic precursor (lipid X) of enterobacterial lipid A. Lipid A synthase from Salmonella accepts not only lipid X but also the synthetic di-N-acyl-2,3-diamino-D-glucose analogue as substrate (Raetz, C.R.H., unpublished results). More and more naturally occurring lipid A's with both, 2,3-diaminoglucose and glucosamine ('mixed' lipid A, with 2,3-diaminoglucose or glucosamine dominating) are being found. Newly recognized lipid A and lipid ADAG types might offer the possibility of differentially stimulating desired biological activities in animals without also having the undesired endotoxic activities. The non-toxic lipid A from Rhodopseudomonas viridis for example is able to stimulate prostaglandin secretion in peritoneal macrophages and can be used as an antagonist to the endotoxic shock caused by Salmonella lipopolysaccharide.
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PMID:Different lipid A types in lipopolysaccharides of phototrophic and related non-phototrophic bacteria. 307 41

We tested the hypothesis that thyrotropin releasing hormone (TRH) would improve cardiovascular function and survival in circulatory shock by opposing the adverse effects of endogenous opioids and other pathophysiologic mediators. Cynomolgus monkeys and mongrel dogs were anesthetized and catheterized to measure mean arterial pressure (MAP) and left ventricular contractility (LV dp/dtmax). Hemorrhagic shock was induced by bleeding into a reservoir to achieve and maintain MAP at 45 mm Hg for one hour. Endotoxic shock was produced by the iv injection of an LD80 dose of Escherichia coli lipopolysaccharide endotoxin (3 mg/kg in dogs and 5 mg/kg in monkeys). Animals were treated iv with either TRH (2 mg/kg plus 2 mg/kg X h) or equivolume saline. TRH significantly increased MAP and LV dp/dtmax in primate hemorrhagic and endotoxic shock. In primate hemorrhagic shock, TRH significantly (p = .02) improved survival (alive/total = 4/5 vs. 0/5). However, TRH had no effect on survival in endotoxemic primates. In contrast, TRH treatment in dogs produced only a transient hemodynamic response after endotoxemia and no significant hemodynamic effect after acute hemorrhage (even at twice the TRH dose). TRH did not affect survival in either dog model of circulatory shock. Based on extensive evidence with the opiate receptor antagonist naloxone in other studies, endogenous opioids play a role in the cardiovascular depression in primate and canine circulatory shock. From these studies with TRH, we conclude that TRH is relatively ineffective in canine circulatory shock, and physiologic antagonism of the adverse effects of opioids and other cardiodepressant substances by TRH administration may prove to be a useful alternative treatment of primate hemorrhagic shock.
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PMID:Thyrotropin releasing hormone: effects in monkeys and dogs subjected to experimental circulatory shock. 310 62

An early-phase tolerance to toxic doses of lipopolysaccharide (LPS) can be induced in mice by prior administration of sublethal doses of LPS or lipid A. These tolerant mice exhibit no hypothermia on subsequent administration of LPS and can survive a challenge dose of LPS that would normally be lethal. Peritoneal exudate cells of LPS-tolerant mice synthesized significantly reduced amounts of prostaglandins and of procoagulant activity (PCA) and tumor necrosis factor (TNF) when stimulated with LPS in vitro (compared to macrophages of control animals). Tolerance induction with lipid A was somewhat less effective. A regulatory mechanism of E-series prostaglandins (PGE) might be involved in the induction of hyporesponsiveness in macrophages of tolerant mice, as the LPS-stimulated TNF release could be inhibited in a dose dependent manner by preincubation with PGE1. Since PCA and TNF are mediators that are proposed to play a very important role in the pathophysiology of septic and endotoxic shock, a reduction in the release of these mediators may be partially responsible for early-phase tolerance to LPS.
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PMID:Reduced release of TNF and PCA from macrophages of tolerant mice. 319 64

Mouse peritoneal macrophages incubated with erythrocytes infected with non-lethal or lethal variants of Plasmodium yoelii or with P. berghei, in the presence of polymyxin B to exclude the effects of any contaminating endotoxin, secreted a cytotoxic factor into the supernatant that was shown to be tumour necrosis factor (TNF). No differences were observed in the ability of the three types of parasite to induce TNF production, which was maximal in the range of 0.2-5 infected erythrocytes per macrophages. TNF production was equivalent to that induced by lipopolysaccharide (LPS) and was enhanced by pretreatment of the macrophages with interferon-gamma (IFN-gamma) or with indomethacin. Culture media containing parasite products also induced macrophages to secrete TNF. The activity withstood boiling and was inhibited by malaria-specific antisera. Since heat-stable antigens are present in the circulation of patients with malaria, they may induced the secretion of TNF, a mediator of endotoxic shock, which could contribute to the pathology of the disease.
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PMID:Malarial parasites induce TNF production by macrophages. 329 8

Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide hormone released in response to bacterial lipopolysaccharide, and it has been implicated as a principal mediator of endotoxic shock, although its function in bacterial sepsis is not known. Anaesthetized baboons were passively immunized against endogenous cachectin and subsequently infused with an LD100 dose of live Escherichia coli. Control animals (not immunized against cachectin) developed hypotension followed by lethal renal and pulmonary failure. Neutralizing monoclonal anti-cachectin antibody fragments (F(ab')2) administered to baboons only one hour before bacterial challenge protected against shock, but did not prevent critical organ failure. Complete protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion. These results indicate that cachectin is a mediator of fatal bacteraemic shock, and suggest that antibodies against cachectin offer a potential therapy of life-threatening infection.
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PMID:Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. 331 66


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