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

Monocytes in a familial monocyte disorder, a recently recognized primary immunodeficiency syndrome, with impaired phagocytic functions were studied for their ability to produce interleukin 1 (IL-1) as well as the surface property. Monocytes from two children (siblings) with the disorder possessed CD11b, CD13, CD14, CD33, Ia and LFA-1/Mac-1/p150,95 beta subunit antigens as determined by flow cytometry. Electron microscopic cytochemistry showed that the monocytes had surface glycoproteins reactive with four representative lectins. The IL-1 production by monocytes was assayed in the two patients and compared with that in six children with primary immunodeficiency syndromes and some monocyte abnormalities; three had congenital neutropenia, two had hyper-IgE syndrome, and one had defective monocyte chemotaxis. Monocyte culture supernatants were prepared with stimulation by lipopolysaccharide or silica, and their IL-1 activity was measured by the mouse thymocyte-proliferation assay. The patients' monocytes were defective in IL-1 production: the values were less than 1.0% of the control monocyte values (n = 12) and were in contrast with those of congenital neutropenia monocytes of 186.2% to 204.3%. These results demonstrate a familial monocyte disorder which is characteristic among the immunodeficiency syndromes with regard to the defective IL-1 production and the impaired phagocytic functions.
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PMID:Defective interleukin-1 production in a familial monocyte disorder with a combined abnormality of mobility and phagocytosis-killing. 326 74

When incubated with lipopolysaccharide (LPS) in the presence of plasma, neutrophils become primed for enhanced release of superoxide in response to triggering by formyl-Met-Leu-Phe (fMLP). The effect of LPS on phagocytes is inhibited by a synthetic lipid A precursor, LA-14-PP (lipid IVa) or by LPS from Rhodobacter sphaeroides (Rs). We studied the mechanisms by which LA-14-PP or Rs-LPS inhibited LPS-induced responses. When neutrophils were exposed to LA-14-PP or Rs-LPS for 3 min and then to Escherichia coli-LPS, the antagonists inhibited priming for superoxide release, and also blocked up-regulation of CD11b and adherence. This inhibition was dependent on plasma, was not overcome by higher amounts of E. coli-LPS or plasma, and was not observed at 0 degrees C, suggesting that E. coli-LPS was not able to interact with its receptor or other cellular recognition molecule in neutrophils that had been exposed to the antagonists. The alternative possibility that LA-14-PP or Rs-LPS depleted a plasma cofactor, resulting in inhibition of priming, was investigated by using LPS from Porphyromonas gingivalis (Pg) and Bordetella pertussis (Bp). These LPS primed neutrophils in a plasma-dependent and CD14-dependent manner, but were not blocked by LA-14-PP or Rs-LPS. When sub-optimal concentrations of plasma were exposed to LA-14-PP or Rs-LPS, and then mixed with Pg-LPS or Bp-LPS, followed by incubation with neutrophils, priming and up-regulation of CD11b were inhibited, and this inhibition was overcome by increasing the concentration of plasma. Binding of LPS-binding protein (LBP) in plasma to immobilized E. coli-LPS was inhibited by pre-incubation of plasma with LA-14-PP or Rs-LPS. Together with the result that treatment of plasma with anti-LBP antibody abolished the cofactor activity of plasma, these results indicated that LA-14-PP and Rs-LPS depleted LBP from plasma, resulting in inability of LPS to act on neutrophils. Thus LA-14-PP and Rs-LPS inhibited the action of LPS on neutrophils by at least two mechanisms, blocking of LPS receptor recognition and depletion of the cofactor LBP.
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PMID:An analogue of lipid A and LPS from Rhodobacter sphaeroides inhibits neutrophil responses to LPS by blocking receptor recognition of LPS and by depleting LPS-binding protein in plasma. 749 65

During the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte-macrophage CSF (rhGM-CSF) we studied the early and late changes of membrane antigen density on neutrophils. RhG-CSF and rhGM-CSF both caused an early transient reduction in blood neutrophilic granulocyte-concentration within the first 30 min after treatment followed by a marked later increase during the subsequent 24 h. During the early neutropenia quantitative flow cytometry showed an associated marked increase in the density of membrane CD11b from 169 x 10(3) before to 568 x 10(3) A.U. per cell induced by rhGM-CSF but a non-significant change by rhG-CSF, suggesting that different mechanisms may be responsible for the transient neutropenia. The subsequent neutrophil granulocytosis was followed by a significantly (P < 0.05) increased density of the CD14 antigen from 6.1 x 10(3) before to 15.9 x 10(3) A.U. per cell during treatment with rhG-CSF, but not by rhGM-CSF administration. These results demonstrate that the two cytokines may affect the function of neutrophilic granulocytes in different ways. The increased expression of CD11b could explain some of the side-effects during treatment with rhGM-CSF. The upregulation of CD14 induced by rhG-CSF may be clinically relevant, as CD14 is an opsonic receptor for lipopolysaccharide binding proteins, acting in the defence against Gram-negative bacterial infections.
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PMID:Different membrane expression of CD11b and CD14 on blood neutrophils following in vivo administration of myeloid growth factors. 750 10

Human neutrophils are primed in the presence of complexes of lipopolysaccharide (LPS) with its serum binding protein (LBP) in a manner dependent on CD14. Cellular consequences of priming include increased responsiveness, the upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac-1), the increased binding of certain ligands to CD11b/CD18, and the concurrent shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18 and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of bacterial endotoxin on the expression of neutrophil adhesive molecules. We observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface numbers and adhesive function of CD11b/CD18 for latex particles, did not induce aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an extent roughly proportional to the available L-selection. Blocking of LPS/LBP with CD14-specific monoclonal antibodies suppressed L-selectin shedding and preserved formyl peptide-stimulated aggregation. Taken together, the data suggest that inhibition of neutrophil aggregation by LPS/LBP is related to the expression of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during cellular stimulation.
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PMID:Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation. 751 6

Previous studies have demonstrated that alveolar macrophages (AMphis) adherent to plastic release interleukin-8 in response to lipopolysaccharide (LPS). We sought to determine whether LPS could also alter surface adhesion molecule expression and thus modulate additional AMphi adhesive interactions. Canine AMphis obtained by bronchoalveolar lavage of excised lung were adhered onto tissue culture plastic and exposed to LPS (0.01 to 100 ng/ml). Expression of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) was subsequently determined by flow cytometry, a cDNA probe to canine ICAM-1 was used to quantify ICAM-1 mRNA, and changes in adhesion molecule function were assessed by evaluating the extent of homotypic aggregation. ICAM-1 and CD11a/CD18 were present on freshly isolated AMphis. CD11b/CD18 and CD11c/CD18 were expressed at lower levels. Nonadherent AMphis expressed a pattern of beta 2 integrin and ICAM-1 comparable to adherent cells. During short-term LPS stimulation (3 h), adherent AMphis increased both the synthesis and expression of ICAM-1. CD18 expression was either decreased or remained unchanged with LPS stimulation. LPS stimulation in vitro (> 0.01 ng/ml) enhanced the homotypic aggregation of adherent AMphis. Aggregation was blocked by monoclonal antibodies to ICAM-1 (CL18/6) and CD11a (R7.1) and CD18 (R15.7). Similar kinetics were found for expression of ICAM-1 and homotypic aggregation, suggesting that up-regulation of ICAM-1 is a major determinant of the LPS-stimulated aggregation of AMphis.
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PMID:Induction of intercellular adhesion molecule-1 by lipopolysaccharide in canine alveolar macrophages. 752 15

In early embryo loss, the fetus may be considered to be an allograft and, therefore, may be rejected by maternal immunocytes. However, the cytotoxic mechanisms involved are still poorly understood. We have previously shown the involvement of natural killer (NK) cells and mononuclear cells expressing Mac-1 (CD11b) and F4/80 in resorbing compared to nonresorbing embryos. In this study, the role of nitric oxide (NO) in the mechanism of early embryo loss was studied. Pregnant CBA/J females mated with DBA/2 males (20-30% early embryo loss) and CD1 females mated with CD1 males (5-10% early embryo loss) were studied on days 8, 10, and 12 of gestation. Cells from the implantation sites of individual embryos were tested for the production of nitrite and nitrate with or without in vitro challenge with lipopolysaccharide (LPS) to determine whether decidual macrophages were primed in situ. On day 12 of gestation, when resorption was clearly visible, resorbing embryos showed more than a fivefold increase in both basal- and LPS-induced nitrite and nitrate production compared to nonresorbing embryos in both mouse strains tested, indicating that the decidual mononuclear cells were primed. Furthermore, more than 20% of CBA/J embryos showed a significant nitrate release on days 8 and 10 of gestation before any signs of embryo cytopathology. This percentage corresponded to the spontaneous resorption rate seen in CBA/J female X DBA/2 male matings. Similarly, 4% of the embryos from pregnant CD1 mice on days 8 and 12 of gestation produced a significant amount of nitrate, which again correlated with the low incidence of resorption observed in these mice. Using immunohistochemistry, the presence of inducible nitric oxide synthase (iNOS) was detected at implantation sites. Furthermore, decidual cells positive for both iNOS and the macrophage marker Mac-1 were demonstrated in implantation sites by double immunostaining. This strongly suggests that decidual macrophages could be the cellular source of NO production. Aminoguanidine, a selective inhibitor of the iNOS, inhibited the in vitro production of nitric oxide by cells isolated from individual implantation sites, and more strikingly, significantly reduced early embryo losses in CBA/J females mated by DBA/2 males when given orally or parenterally to the gravid females starting on day 6 of gestation. In addition, aminoguanidine-treated pregnant mice showed a significant increase in average litter size when the pregnancies were allowed to proceed to term.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Early embryo loss is associated with local production of nitric oxide by decidual mononuclear cells. 756 87

Extravasation of leukocytes at sites of ischemia may mediate tissue injury. To determine how leukocyte accumulation may be induced by ischemia, effects of hypoxia on basal neutrophil expression of adhesion and activation receptors were examined. Effects of hypoxia upon preactivated cells were also studied. To determine whether regulation of expression is dependent on oxygen availability or on mitochondrial respiration, the effects of physical hypoxia (substitution of O2 by nitrogen) were compared with those of chemical hypoxia with sodium cyanide (NaCN). Leukocytes in whole blood (eight volunteers) were exposed either to hypoxia alone or to priming concentrations of lipopolysaccharide (LPS, 1 microgram/ml) followed by chemical hypoxia (NaCN, 1 mM) or physical hypoxia (PO2 of 1-10 torr) for various time intervals. Room air was controlled and hypoxic cells were labeled with fluorescent monoclonal antibodies to integrins CD18 and CD11b or to the 55-kDa TNF alpha cell surface receptor (TNFR). Receptor concentrations were measured by flow cytometry. Data were analyzed by ANOVA/Student's t test. Physical hypoxia increased expression of both CD11b and CD18 over time and augmented their LPS-induced up-regulation. Isolated chemical hypoxia did not change neutrophil expression of CD11b or CD18, but partially inhibited neutrophil CD11b and CD18 up-regulation by LPS. LPS-induced TNFR down-regulation was not affected by physical hypoxia, which failed to alter TNFR expression in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypoxia-induced alterations of neutrophil membrane receptors. 763 Jan 18

Factors in circulating air may play a role in immune responses after surgery through induction of gut-derived lipopolysaccharide (LPS) translocation across the gut. CD-1 mice were randomized to one of four treatment groups: controls, laparoscopy with carbon dioxide inflation, laparoscopy with air inflation and laparotomy. The peritoneal and systemic immune response was assessed by evaluating peritoneal macrophage, blood monocyte and neutrophil activity. In a second study, the effect of each of the treatments on fluorescein isothiocyanate (FITC)-LPS translocation across the gut was assessed. There were significant (P < 0.05) increases in peritoneal tissue macrophage release of superoxide and tumour necrosis factor after laparoscopy with air and laparotomy compared with control procedures and carbon dioxide laparoscopy. However, peritoneal macrophage FITC-Candida albicans ingestion was significantly decreased after air laparoscopy and laparotomy compared with controls and carbon dioxide laparoscopy (P < 0.05). These findings correlated with a significant (P < 0.05) decrease in CD11b expression. Significant translocation into the peritoneal cavity and systemic circulation occurred after air laparoscopy and laparotomy only. Factors in circulating air can induce LPS translocation and subsequent stimulation of postoperative immune responses. The beneficial effects of laparoscopic surgery may be explained by the minimal air contamination of the peritoneal cavity.
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PMID:Exposure of the peritoneal cavity to air regulates early inflammatory responses to surgery in a murine model. 764 54

Vascular endothelial injury observed in overwhelming sepsis may be caused by neutrophil-derived enzymes. Adherence to the endothelium, a prerequisite for this process, is mediated sequentially by the neutrophil adhesion molecules L-selectin and the beta 2 integrins including CD11b/CD18. The relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury was assessed by changes in heparan sulfate and fibronectin matrices. Endothelial prestimulation with lipopolysaccharide caused both an increase in adherence and a generalized reduction in heparan sulfate; disruption of the fibronectin matrix occurred only on the further addition of FMLP. Although maximal disruption of these matrices was associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. This model may provide further insights into the interrelationship between neutrophil activation and endothelial damage in gram-negative sepsis.
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PMID:Degradation of glycosaminoglycans and fibronectin on endotoxin-stimulated endothelium by adherent neutrophils: relationship to CD11b/CD18 and L-selectin expression. 768 Jul

Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to examine the LPS-induced production of tumor necrosis factor alpha and interleukin-6 in PNH patients and healthy volunteers. At low endotoxin concentrations (1 ng/ml), PNH patients displayed a marked defect in the production of both cytokines, whereas at high LPS concentrations (100 ng/ml), cytokine production was similar to that in healthy volunteers. Using flow cytometry, we also studied the expression of the adhesion molecules Mac-1 (CD11b/CD18) and ICAM-1 (CD54) by monocytes and granulocytes after LPS stimulation. Compared with phagocytes from healthy volunteers, CD14-deficient cells showed poor Mac-1 and ICAM-1 upregulation when whole blood was stimulated with LPS (1 ng/ml), whereas their response to higher LPS doses (100 and 1,000 ng/ml) was essentially normal. The importance of the CD14 molecule in the activation of phagocytes by low LPS concentrations was confirmed by the inhibitory effect of an anti-CD14 antibody both in healthy volunteers and in PNH patients. Since these patients produce the soluble form of the CD14 molecule, these data suggest that soluble CD14 could play a role in phagocyte responses to LPS. We conclude that, in whole blood, phagocytes from PNH patients show impaired responsiveness to LPS and this phenomenon is most probably related to their defect in expression of membrane CD14.
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PMID:Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria. 769 46


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