Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in situ inflammatory response developing in the human lung during a localized bacterial infection was studied in 15 patients with unilateral community-acquired pneumonia (CAP). The local response in the involved lung was compared with that in the contralateral, noninvolved lung as well as with the systemic blood response. Eight healthy volunteers served as control subjects. Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA in bronchoalveolar lavage (BAL) fluids (n = 15), serum (n = 15), and alveolar macrophage and monocyte culture supernatants (n = 8). The concentrations of TNF-alpha, IL-beta and IL-6 in BAL fluid were significantly higher in the involved lung than in the paired noninvolved lung (p < or = 0.01) or in healthy subjects (p < or = 0.02, p < or = 0.01, and p < or = 0.001, respectively). Serum IL-6 concentrations were higher in patients than in control subjects, whereas IL-1 beta and TNF-alpha concentrations did not differ in the two groups. Alveolar macrophages from the involved lung spontaneously released higher concentrations of IL-1 beta, IL-6, and TNF-alpha (p < or = 0.05) than did macrophages from the noninvolved lung, which served as controls. However, macrophages were hyporesponsive in terms of cytokine production to further stimulation by lipopolysaccharide (LPS) in the noninvolved and involved lung compared with controls, whereas peripheral blood monocytes were not.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Compartmentalized cytokine production within the human lung in unilateral pneumonia. 808 41

Endotoxin (lipopolysaccharide [LPS]) released during gram-negative bacterial infection induces varieties of cytokines which directly and/or indirectly cause shock, disseminated intravascular coagulation, and death. We previously showed that lysozyme (LZM) was an LPS-binding protein and inhibited various immunomodulating activities of LPS. In this study, we examined the effect of LZM on the LPS-triggered septic shock model induced by carrageenan treatment and assessed by tumor necrosis factor production. The data presented in this report strongly suggest that LZM-LPS complex formation completely abrogates tumor necrosis factor production and the mortality caused by LPS and that LZM may be useful for the treatment of endotoxin shock.
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PMID:Binding of lysozyme to lipopolysaccharide suppresses tumor necrosis factor production in vivo. 813 23

Newborn infants are more susceptible to bacterial infections than adults. This susceptibility has been attributed to defects in humoral and cellular activity. Host cellular activity can be modified by factors produced by bacteria or the host in response to infection. We assessed the effect of two factors associated with gram-negative bacterial infection, lipopolysaccharide (LPS) and TNF-alpha, on polymorphonuclear neutrophilic granulocytes (PMN) obtained from adult or newborns (umbilical cord blood). PMN were primed in vitro with LPS (10 micrograms/L) or TNF-alpha (10(-9) M) for 45 min and then assessed, using a chemiluminescence (CL) assay as an indicator of oxidative radical production with formyl-methionyl-leucyl-phenylalanine as the trigger for CL initiation. CL activity of unprimed PMN was similar for adults and newborns (13.3 and 13.7 CL units, respectively). After priming with LPS, CL activity was increased to 43.4 CL units for PMN from adults but to only 17.6 CL units for PMN from newborns (p < 0.001, adults versus newborn increment). Priming of PMN with LPS was most effective when autologous plasma was present. Using FITC-conjugated LPS and a flow cytometry assay, we could demonstrate no difference between the binding affinity of LPS for adult and newborn PMN. However, formyl-methionyl-leucyl-phenylalanine binding studies indicated that adult PMN had a higher number of binding sites. TNF-alpha priming of newborn PMN was also ineffective. Adult PMN increased CL activity by 3.9-fold when primed with TNF-alpha, whereas newborn PMN increased by only 1.75-fold (p < 0.005). This priming deficiency was not attributable to TNF-alpha receptors because phycoerythrin-conjugated TNF-alpha was associated with PMN from adults and newborns equally. Thus, PMN from newborns are not primed effectively in vitro with LPS or TNF-alpha. This defect may contribute to neonatal susceptibility to bacterial infection.
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PMID:Deficient priming activity of newborn cord blood-derived polymorphonuclear neutrophilic granulocytes with lipopolysaccharide and tumor necrosis factor-alpha triggered with formyl-methionyl-leucyl-phenylalanine. 813 62

Bactericidal/permeability-increasing protein (BPI), a cationic protein found in neutrophil granules, binds with high affinity to gram-negative bacterial lipopolysaccharide (LPS) and can inhibit its actions in vitro. The in vivo efficacy of a recombinant 23-kDa amino-terminal LPS-binding fragment of BPI (rBPI23) was assessed in a mouse model of lethal endotoxemia. Systemic administration of rBPI23 protected actinomycin D-sensitized mice from lethal LPS (Escherichia coli O111:B4) challenge in a dose-dependent manner, with almost complete protection at the highest dose (10 mg/kg; 93% survival vs. 13% in vehicle-treated controls). Surviving rBPI23-treated animals did not show histopathologic signs of tissue damage evident in control animals that had died after LPS challenge. rBPI23 also attenuated the LPS-induced elevation in serum levels of tumor necrosis factor-alpha and interleukin-1 alpha, mediators believed to be involved in the pathogenesis of endotoxemia and sepsis. Thus, rBPI23 may be a potential new therapeutic agent for the treatment of gram-negative bacterial infection and sepsis.
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PMID:Protective effect of a recombinant amino-terminal fragment of bactericidal/permeability-increasing protein in experimental endotoxemia. 822 69

Overwhelming bacterial infection is accompanied by fever, hypotension, disseminated intravascular coagulation, and multiple organ failure leading to death in 30-80% of cases. These classical symptoms of septic shock are caused by potent cytokines that are produced in response to endotoxin released from Gram-negative bacteria. Treatments with antibodies and receptor antagonists to block endotoxin or cytokine mediators have given mixed results in clinical trials. High density lipoprotein (HDL) is a natural component of plasma that is known to neutralize endotoxin in vitro. We report here that raising the plasma HDL concentration protects mice against endotoxin in vivo. Transgenic mice with 2-fold-elevated plasma HDL levels had more endotoxin bound to HDL, lower plasma cytokine levels, and improved survival rates compared with low-HDL mice. Intravenous infusion of HDL also protected mice, but only when given as reconstituted HDL prepared from phospholipid and either HDL apoprotein or an 18-amino acid peptide synthesized to mimic the structure of apolipoprotein A-I of HDL. Intact plasma HDL was mildly toxic, and HDL apoprotein was ineffective. The effectiveness of the reconstituted peptide renders very unlikely any significant contribution to protection by trace proteins in apo-HDL. These data suggest a simple leaflet insertion model for binding and neutralization of lipopolysaccharide by phospholipid on the surface of HDL. Plasma HDL may normally act to protect against endotoxin; this protection may be augmented by administration of reconstituted HDL or reconstituted peptides.
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PMID:In vivo protection against endotoxin by plasma high density lipoprotein. 826 67

Interleukin (IL)-8 is a macrophage-derived neutrophil chemotactic factor that plays an important role in the recruitment of neutrophils to inflammatory loci. Hence, expression of IL-8 by alveolar macrophages may be a significant factor in host defense in the lung and in the pathogenesis of pneumonia in swine. To initiate molecular studies of IL-8 regulation in pigs, we cloned IL-8 cDNA and examined the regulation of its mRNA in alveolar macrophages. The porcine IL-8 cDNA consists of 1491 base pairs including a coding region of 309 base pairs. The deduced amino acid sequence was 75 and 81% similar to human and rabbit IL-8, respectively. Resting macrophages contained low levels of IL-8 mRNA, which increased markedly after exposure to bacterial lipopolysaccharide (LPS). LPS induction of IL-8 was direct, not mediated through elevation of tumor necrosis factor or interleukin-1. The effect of LPS on IL-8 expression was dose dependent, and induction was observed at a concentration of 10 pg/ml. IL-8 mRNA expression was detectable within 0.5 h after stimulation with LPS, peaked at 3-6 h at about 30-fold higher levels than in resting cells, and was maintained for 24 h. Secreted IL-8, measured by neutrophil chemotaxis, was induced within 4 h by LPS, and accumulated in the media throughout the 24-h period. The mechanism of induction of IL-8 mRNA appeared to involve transcription and RNA processing. Nuclear run-on analysis showed that the IL-8 gene was actively transcribed in noninduced cells; upon stimulation with LPS, the rate of IL-8 transcription was increased about 4-fold. A single mature mRNA species was detected by primer extension analysis. The half-life of IL-8 mRNA transcripts in aveolar macrophages was approximately 2 h and did not change after LPS stimulation. The ability of LPS to induce IL-8 expression was suppressed by recombinant human IL-4 and dexamethasone in a concentration-dependent manner. These observations indicate that the expression of IL-8 is an early event in the sequelae to bacterial infection in the lung.
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PMID:Regulation of interleukin-8 expression in porcine alveolar macrophages by bacterial lipopolysaccharide. 827 81

A novel fluorescence assay for phospholipase A2 [Wilton (1990) Biochem. J. 266, 435-439] has been used to study the Group-II rat liver mitochondrial enzyme, and a number of novel properties of this enzyme were identified. (1) The enzyme activity was located in the liver macrophages (Kupffer cells) while negligible activity was associated with hepatocytes. (2) Although subcellular fractionation of whole liver confirmed the predominantly mitochondrial location of this enzyme activity, the analysis of the hepatocyte-free Kupffer-cell-enriched fraction revealed a different enzyme distribution, with the majority of activity being associated with the microsomal membrane fraction. (3) Bacterial endotoxin has been previously shown to be scavenged by Kupffer cells in rats. Treatment of rats with bacterial lipopolysaccharide (endotoxin) resulted in a dramatic time- and dose-dependent increase in liver phospholipase A2 activity. (4) It is known that injection of endotoxin into rodents results in elevated serum phospholipase A2 activity, while a similar phenomenon is seen in the condition of septic shock in man. The source of this serum enzyme was unknown. In this study perfusion of livers from rats pretreated with lipopolysaccharide with physiological saline demonstrated a 6-fold increase in phospholipase A2 activity in the perfusate compared with sham-treated controls, with only minor release of hepatic lipase. (5) Western-blot analysis confirmed an increased release of this Group-II phospholipase A2 into the perfusate of lipopolysaccharide-treated rats compared with sham-treated controls. These results suggest that liver Kupffer cells are a major source of the endotoxin-induced serum Group-II phospholipase A2 activity associated with bacterial infection and trauma.
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PMID:Rat liver mitochondrial phospholipase A2 is an endotoxin-stimulated membrane-associated enzyme of Kupffer cells which is released during liver perfusion. 832 56

Triacylglycerols in human neutrophils exposed to proinflammatory stimuli generate a high-resolution proton magnetic resonance (1H MR) spectrum. Lipid cross-peak F volumes in neutrophils from patients with inflammatory conditions were measured. Values in patients hospitalized with localized infections (14.4 +/- 9.0; mean +/- SD) or bacteremia (19.3 +/- 9.7) were significantly higher than in patients with noninflammatory conditions (6.2 +/- 5.3) and healthy controls (2.0 +/- 3.0; P < .001). The positive predictive value of F volumes > 10 was 93% for all infection; the negative predictive value of volumes < or = 10 was 68% for all infection and 92% for bacteremia. Plasma lipopolysaccharide (LPS) concentrations were highest in bacteremic patients but did not correlate with levels of tumor necrosis factor-alpha (TNF alpha) or interleukin-6. In vitro, LPS increased F volumes of control neutrophils from 2.0 +/- 3.0 to 37.2 +/- 6.7 (P < .001); TNF alpha had no effect. F volumes in 1H MR spectra may be useful clinically to discriminate between serious bacterial infection and other inflammatory conditions. TNF alpha is not the stimulus for generation of lipid spectra in vivo.
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PMID:Proton magnetic resonance spectroscopy of polymorphonuclear leukocytes from patients with serious bacterial infections. 833 75

In the acute phase of bacterial infection, a variety of cytokines, including interleukin-1 (IL-1), are elicited by bacterial endotoxin in both the periphery and the central nervous system. Bacterial endotoxin has been previously reported to profoundly activate the hypothalamic-pituitary-adrenal axis, resulting in elevated glucocorticoid secretion that may serve an important role as part of the inhibitory feedback mechanisms on the activated immune system. To determine whether IL-1 acts within the brain to mediate endotoxin-induced CRH gene expression in the hypothalamic paraventricular nucleus (PVN), we studied the effect of administering the human IL-1 receptor antagonist (IL-1ra) into the brain, a competitive inhibitor of IL-1, on CRH gene expression in the PVN after systemic lipopolysaccharide (LPS) treatment. Eight hours after the ip administration of LPS, the paraventricular CRH mRNA content was elevated 3-to 4-fold (P < 0.01) compared to the control value, and this elevation could be completely abolished by central IL-1ra pretreatment (P < 0.05 compared to LPS-treated group; P > 0.05 compared to controls). In contrast, systemic IL-1ra administration did not inhibit endotoxin-induced CRH gene expression in the PVN. These studies demonstrate that LPS stimulates hypothalamic CRH by a mechanism that involves the action of IL-1 within the central nervous system and may proceed independently of peripheral actions of IL-1 circulating in the bloodstream.
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PMID:Endotoxin-induced corticotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is mediated centrally by interleukin-1. 834 18

The murine Cr2 gene encodes mRNA that produce two protein products predicted to be approximately 145,000 M(r) (Cr2-145) and 190,000 M(r) (Cr2-190). All cells examined which express the Cr2 gene produce transcripts encoding both the Cr2-145 and Cr2-190 proteins: both transcripts are constitutively expressed by mature B cells. To determine if Cr2 expression could be altered by activating splenic B cells, splenic cultures were incubated with lipopolysaccharide (LPS) and cell surface Ig chains were cross-linked with anti-mu. In the presence of LPS and anti-mu both Cr2 and Oct-2 transcripts were diminished while the control beta-actin transcript levels remained unchanged. However, when LPS alone was added, only the Cr2 transcript levels were diminished. To test if these findings could be reproduced in vivo, animals were provided with a peritoneal injection of either Escherichia coli or Listeria monocytogenes and transcript levels analysed. The quantities of both Cr2 transcripts, as well as those encoding Oct-2, were substantially reduced in splenocytes and peripheral lymphatic tissues obtained from these infected mice while those encoding the mouse Crry protein, the B-cell marker CD19 and beta-actin remained unchanged. These data suggest that when confronted with a major bacterial infection, murine B cells respond by shutting down synthesis of transcripts encoding the Cr2 and Oct-2 gene products.
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PMID:Murine complement receptor gene expression: Cr2 gene transcripts are depressed during a high dose microbial challenge. 850 45


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