UNIPROT:P43026 - FACTA Search

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

The mortality of sepsis/septic shock continues to be high in newborns. However, there is no established method in its treatment. Although calcium channel blockers ameliorate the hemodynamic deterioration of adult circulatory shock, their effects on newborn endotoxic shock have not been elucidated. This study was performed in newborn dogs to investigate the effects of diltiazem on newborn endotoxic shock. Endotoxic shock was induced in newborn dogs (2-10 days old, 300-800 g) by an intravenous injection of E. coli lipopolysaccharide (LPS; 1.5 mg/kg), and diltiazem (DZ) at the dose of 300, 600 or 1200 micrograms/kg was administered intravenously 20 min prior to LPS injection. Hemodynamic changes were serially observed until 120 min after LPS injection. The heart rate, mean arterial pressure and cardiac output decreased after LPS injection, and systemic vascular resistance decreased. DZ at the dose of 600 micrograms/kg attenuated the decreases of MAP and cardiac output, but 300 and 1200 micrograms/kg of DZ exacerbated them. DZ at the dose of 1200 micrograms/kg decreased the heart rate, and DZ at all three doses attenuated the increase of systemic vascular resistance. Therefore, 600 micrograms/kg of DZ is beneficial in the treatment of endotoxic shock in newborn dogs.
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PMID:Diltiazem treatment in newborn canine endotoxic shock. 208 81

Alveolar macrophages (AM) from lungs of normal F344 rats can be rendered tumoricidal by incubation in vitro with either muramyl dipeptide (MDP) at a minimum dose of 10 micrograms/ml or undiluted cell-free culture supernatants from mitogen-stimulated F344 rat lymphocytes rich in macrophage-activating factor (MAF) activity. Neither MAF at dilutions exceeding 1:6 nor MDP at doses lower than 10 micrograms/ml activated AM to become tumor cytotoxic. The combination of agents at subthreshold amounts (MAF 1:18; MDP 0.001 to 1 microgram/ml) activated AM to significant levels of cytotoxicity. AM activated by these agents were rendered tumoricidal and destroyed syngeneic, allogeneic, and xenogeneic tumor targets in vitro. The synergism for AM activation between preparations of MAF and MDP required that AM be incubated first with MAF and then with MDP. Even a 15-min treatment of AM with MAF conditioned the cells to respond to subthreshold amounts of MDP and to be rendered tumoricidal. Since treatment of MAF and MDP with polymyxin B did not interfere with macrophage activation, we were able to rule out the possibility that our preparations were contaminated with lipopolysaccharide. Synergism for AM activation was demonstrated also when AM were treated with MAF and MDP encapsulated within liposomes. This finding suggests that the binding of agents to the macrophage surface is not a prerequisite for the synergistic activation of AM by MAP and MDP.
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PMID:Synergistic activation by lymphokines and muramyl dipeptide of tumoricidal properties in rat alveolar macrophages. 743 Jun 35

Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY. Second, in rats rendered hypotensive by intravenous LPS, continuous NE infusion (0.1-1.0 microgram.kg-1 x min-1 started 5 min after LPS for 1 h) did not alter hemodynamics. In contrast, 5 nmol.kg-1 x min-1 of NPY (equipotent to 0.1 microgram.kg-1 x min-1 of NE in normal rats) increased mean arterial pressure (MAP, from 64 to 114% of baseline), total peripheral resistance index (TPRI, from 64 to 154% of baseline), and left ventricular stroke work index (from 36 to 73% of baseline), without changing cardiac index (CI). Third, in a similar experimental protocol, pretreatment of the hypotensive rats with phentolamine blocked the pressor effect of NE infusion, but only partially attenuated the response to NPY. Finally, addition of low-dose NPY to NE infusion improved survival following a lethal dose of LPS compared with treatment with NE alone (P < 0.01). Thus, unlike other vasoconstrictors tested, NPY-mediated vasoconstriction is preserved during endotoxemia. The beneficial effect of NPY is mediated by increased TPRI without reduction in CI; both NPY receptor-mediated vasoconstriction and potentiation of adrenergic responsiveness may be involved.
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PMID:Neuropeptide Y infusion improves hemodynamics and survival in rat endotoxic shock. 790 7

A reconstituted lipoprotein, containing human apolipoprotein A-I and phosphatidylcholine (1:200, molar ratio), referred to as ApoLipo, was used prophylactically in an endotoxin shock model in anesthetized rabbits. ApoLipo was administered at a dose of 75 mg protein/kg body weight 15 min before the beginning of a slow, continuous lipopolysaccharide (LPS, endotoxin) infusion (4.17 micrograms LPS/kg/hr). During the 6 hr LPS infusion, the Control-LPS group manifested a marked increase in serum tumor necrosis factor (TNF, peak value 7.82 [2.7-11.2] ng/ml at 1 hr), and many of the pathophysiologic sequelae of endotoxin shock, including hypotension (MAP: 59 +/- 7 mmHg) and metabolic acidosis (BE: -9.9 +/- 2.7) at 3 hr, and a severe neutropenia developed rapidly (PMN count: 5 +/- 3% of baseline at 30 min). In the ApoLipo treated group, serum TNF levels did not rise during the course of LPS infusion (0.1 [0.06-0.64] ng/ml at 1 hr). Hypotension (77 +/- 2 mmHg) and acidosis (-2.7 +/- 0.4) were also significantly attenuated, and the appearance of leukopenia was delayed by 1 hr (110 +/- 12% at 30 min, but 9 +/- 2% at 2 hr). Endotoxemia in the ApoLipo treated group was reduced in comparison to controls, albeit nonsignificantly. The infusion of the same dose of phosphatidylcholine without apoA-I was significantly less efficacious.
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PMID:A reconstituted, apolipoprotein A-I containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. 832 86

Although various mediators such as platelet activating factor, anaphylatoxin and cytokines are considered to be involved in the pathology of endotoxin-induced shock, an endothelium-derived relaxing factor (EDRF), nitric oxide (NO) or its related substance, has recently been shown as a vasodilating factor that is produced from L-arginine. On the other hand, NG-nitro-L-arginine (L-NNA) is shown to inhibit NO production from L-arginine. Thus, in order to examine a possible involvement of NO in the shock, the effect of L-NNA administration was studied on the hemodynamics and plasma hormone levels during endotoxin-induced shock in anesthetized dogs. Twenty-five mongrel dogs were divided into the following 5 groups; (1) In group C, only physiological saline was administered. (2) In group L, a bolus injection of L-NNA (4 mg/kg B.W.) was followed by a continuous infusion of the agent (0.05 mg/kg B.W./min) for 120 min. (3) In group E, lipopolysaccharide (LPS) E. Coli 011:B4 2.625 mg/kg body weight was administered. (4) In group LE, L-NNA administration (bolus and continuous) the same as in group L was started 5 min before the injection of LPS. (5) In group EL, L-NNA administration (bolus and continuous) was started 5 min after the injection of LPS. In Group LE, MAP decreased to -45.9 mmHg 5 min after LPS injection and -33.0 mmHg 120 min from pre-level. The levels of MAP from 15 to 90 min were significantly higher than those in Group E. In Group EL, MAP decreased to -61.4 mmHg 5 min after LPS injection and this low level (-59.5 mmHg) continued for 120 min. A protecting effect of L-NNA against LPS-induced hypotension was clearly observed only when administration of the agent was started before LPS injection. These results indicated that LPS induced shock could be produced by a possible increase of NO production in the vascular endothelial cells. The other finding in the present experiment using anesthetized animals was that L-NNA had a stimulatory action on some endocrine systems such as the renin-aldosterone system and pituitary-adrenal axis, although the exact mechanism of this action of L-NNA on such systems was unclear.
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PMID:[The effect of NG-nitro-L-arginine administration on the hemodynamics and plasma hormone levels during endotoxin shock in dogs]. 838 33

1. The aims of the present study were to determine the profile of tumour necrosis factor (TNF) release, and the effect of monoclonal antibodies to TNF, on the changes in regional haemodynamics and the responses to vasodilator and vasoconstrictor challenges, during a continuous 24 h low dose infusion of lipopolysaccharide (LPS) in conscious rats. 2. Male Long Evans rats were chronically instrumented for measurement of regional haemodynamics (renal, superior mesenteric and hindquarters) and were challenged with 3 min infusions of acetylcholine (22 nmol min-1), methoxamine (120 nmol min-1), salbutamol (0.83 nmol min-1) and bradykinin (14.4 nmol min-1). The rats were given either saline, or the TNF antibodies, TN3g1 or TN3g2a, 1 h before the start of a continuous infusion of LPS (150 micrograms kg-1 h-1) and were subsequently re-tested with the vasodilator and vasoconstrictor challenges 2, 6 and 24 h after the start of the LPS infusion. 3. Prior to infusion of LPS, TNF was not detectable in the plasma. During continuous infusion of LPS there was a transient elevation in plasma TNF levels, reaching a maximum (approximately 2300 pg ml-1) after approximately 1 h, and returning to undetectable levels after approximately 3 h of LPS infusion. 4. In the saline pretreated group, after 1-2 h of LPS infusion, there was a small hypotension and a marked renal vasodilation; 6 h after the start of LPS infusion there was a minor elevation in MAP above control levels, renal vasodilatation was maintained and a hindquarters vasoconstriction occurred; after 24 h of LPS infusion, there was a hypotension and renal and hindquarters vasodilatation. There were significant reductions in the tachycardic and renal vasodilator responses and an enhanced depressor response to acetylcholine after 24 h of LPS infusion. LPS infusion also caused a generalized hyporesponsiveness to the cardiovascular effects of methoxamine and salbutamol. The major changes in response to bradykinin were reduced tachycardic and enhanced depressor responses throughout the LPS infusion, a biphasic decrease and increase in renal conductance and enhanced hindquarters vasodilatation at 24 h. 5. Pretreatment with either TN3g1 or TN3g2a antibodies had no major effects on the changes in resting haemodynamics, or on the changes in response to methoxamine, salbutamol or bradykinin challenges during LPS infusion. However, the tachycardic responses to acetylcholine were generally preserved, and its hypotensive effect after 24 h of LPS infusion was not enhanced after TN3g1 or TN3g2a pretreatment. Thus, despite substantial, but transient, elevation of plasma TNF levels during continuous LPS infusion, it appears that the majority of cardiovascular changes were dependent on factors other than plasma TNF.
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PMID:Lack of effect of TNF antibodies on the cardiovascular sequelae of lipopolysaccharide infusion in conscious rats. 858 Dec 89

The addition of platelet-activating factor (PAF) to human neutrophils increases phosphorylation on tyrosine residues and stimulates the activity of p42erk2 mitogen-activated protein kinase (MAP kinase). This action is rapid and transient. In contrast, p42erk2, p44erk1 and the p40hera MAP kinase isoforms are all not tyrosine phosphorylated or activated in human neutrophils stimulated with low concentrations of lipopolysaccharide (LPS) in combination with serum. In spite of this, the PAF-induced tyrosine phosphorylation and activation of the p42erk2 MAP kinase are greatly potentiated in cells pretreated with LPS. More interestingly, although low concentrations of LPS do not affect MAP kinase isoforms in these cells, they cause the phosphorylation of cytosolic phospholipase A2 (cPLA2), as evidenced by a decrease in the electrophoretic mobility of the enzyme. In addition, this stimulus-induced upward shift in the mobility of the enzyme is not inhibited by the tyrosine kinase inhibitor, genistein. Furthermore, LPS increases the release of arachidonic acid in control and PAF-stimulated human neutrophils. These observations clearly show that cPLA2 can be phosphorylated and activated by kinases other than the currently known MAP kinases. It is proposed that there are MAP kinase-dependent and -independent mechanisms for the phosphorylation of cPLA2.
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PMID:Effect of lipopolysaccharide on mitogen-activated protein kinases and cytosolic phospholipase A2. 894 37

1. This study investigated the effects of low dose endotoxin (lipopolysaccharide, LPS) on (i) systemic haemodynamics, (ii) renal blood flow (RBF), (iii) renal cortical and medullary perfusion and (iv) renal function in the anaesthetized rat. We have also investigated the effects of nitric oxide (NO) synthase (NOS) inhibition with NG-methyl-L-arginine (L-NMMA) on the alterations in systemic and renal haemodynamics and renal function caused by endotoxin. 2. Infusion of low dose LPS (1 mg kg-1 over 30 min, n = 6) caused a late fall in mean arterial blood pressure (MAP, at 5 and 6 h after LPS), but did not cause an early (at 1-4 h after LPS) hypotension. The pressor effect of noradrenaline (NA, 1 microgram kg-1, i.v.) was significantly reduced at 1 to 6 h after LPS (vascular hyporeactivity). Infusion of L-NMMA (50 micrograms kg-1 min-1 commencing 60 min before LPS and continued throughout the experiment, n = 7) abolished the delayed hypotension and significantly attenuated the vascular hyporeactivity to NA (at 2-6 h). 3. Infusion of LPS (1 mg kg-1 over 30 min, n = 6) caused a rapid (within 2 h) decline in renal function (measured by inulin clearance) in the absence of a significant fall in MAP or renal blood flow (RBF). L-NMMA (n = 7) attenuated the impairment in renal function caused by LPS so that the inulin clearance in LPS-rats treated with L-NMMA was significantly greater than in LPS-rats treated with vehicle (control) at 3-6 h after infusion of LPS. 4. Endotoxaemia also caused a significant reduction in renal cortical, but not medullary perfusion (measured as Laser Doppler flux). Infusion of L-NMMA caused a significant further fall in cortical perfusion and a significant fall in medullary perfusion in the absence of changes in RBF. 5. Infusion of LPS resulted in a progressive increase in the plasma levels of nitrite/nitrate (an indicator of the formation of NO), so that the plasma concentration of nitrite/nitrate was significantly higher than baseline at 150 to 330 min after LPS. Infusion of L-NMMA attenuated the rise in the plasma concentration of nitrite/nitrate (at 270 and 330 min, P < 0.05) caused by LPS. 6. Thus, the renal dysfunction caused by injection of low dose of endotoxin in the rat occurs in the absence of significant falls in blood pressure or total renal blood flow. Inhibition of NOS activity with L-NMMA attenuates the renal dysfunction caused by endotoxin (without improving intrarenal haemodynamics), suggesting that an overproduction of NO may contribute to the development of renal injury and dysfunction by causing direct cytotoxic effects.
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PMID:Intrarenal haemodynamics and renal dysfunction in endotoxaemia: effects of nitric oxide synthase inhibition. 928 24

Receptors on macrophages for the Fc region of IgG (FcgammaR) mediate a number of responses important for host immunity. Signaling events necessary for these responses are likely initiated by the activation of Src-family and Syk-family tyrosine kinases after FcgammaR cross-linking. Macrophages derived from Syk-deficient (Syk-) mice were defective in phagocytosis of particles bound by FcgammaRs, as well as in many FcgammaR-induced signaling events, including tyrosine phosphorylation of a number of cellular substrates and activation of MAP kinases. In contrast, Syk- macrophages exhibited normal responses to another potent macrophage stimulus, lipopolysaccharide. Phagocytosis of latex beads and Escherichia coli bacteria was also not affected. Syk- macrophages exhibited formation of polymerized actin structures opposing particles bound to the cells by FcgammaRs (actin cups), but failed to proceed to internalization. Interestingly, inhibitors of phosphatidylinositol 3-kinase also blocked FcgammaR-mediated phagocytosis at this stage. Thus, PI 3-kinase may participate in a Syk-dependent signaling pathway critical for FcgammaR-mediated phagocytosis. Macrophages derived from mice deficient for the three members of the Src-family of kinases expressed in these cells, Hck, Fgr, and Lyn, exhibited poor Syk activation upon FcgammaR engagement, accompanied by a delay in FcgammaR-mediated phagocytosis. These observations demonstrate that Syk is critical for FcgammaR-mediated phagocytosis, as well as for signal transduction in macrophages. Additionally, our findings provide evidence to support a model of sequential tyrosine kinase activation by FcgammaR's analogous to models of signaling by the B and T cell antigen receptors.
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PMID:A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages. 931 52

The influence of osmolarity and compatible organic osmolytes on the phosphorylation of the MAP-kinases Erk-1 and Erk-2 and on the expression of taurine transporter (TAUT) and lipopolysaccharide (LPS)-induced nitric oxide synthetase (iNOS) was studied in RAW 264.7 mouse macrophages. Hypoosmolarity (205 mosmol/l) but not hyperosmolarity (405 mosmol/l) or challenge of the cells with betaine or taurine increased phosphorylation of Erk-1 and Erk-2. Hypoosmotic Erk-phosphorylation was blocked by the MEK-inhibitor PD098059 but was resistant to depletion of extracellular calcium and to inhibition of PLC, PKC, erbstatin-sensitive tyrosine kinases and elevation of intracellular cAMP. Hyperosmolarity stimulated Na+-dependent taurine uptake and led to an increase of TAUT mRNA levels, whereas hypoosmotic exposure diminished both and induced a rapid efflux of the osmolyte from taurine-preloaded cells. The hyperosmotic elevation of TAUT mRNA levels was antagonized upon addition of taurine but not of betaine or myo-inositol. Hyperosmolarity increased the LPS-induced iNOS expression at the mRNA and the protein level. This was suppressed by betaine but not by taurine or myo-inositol. The osmotic regulation of taurine transport and iNOS expression appeared independent of the MEK-Erk pathway and the p38MAPK.
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PMID:Compatible organic osmolytes and osmotic modulation of inducible nitric oxide synthetase in RAW 264.7 mouse macrophages. 970 50

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