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)

Human monoclonal IgM antibody HA-1A, which recognizes the lipid A component of bacterial lipopolysaccharide (LPS), has been shown to reduce mortality in Gram negative septicemia. The vascular endothelial lining of blood vessels, which controls leucocyte traffic and activation, as well as haemostatic balance, may be one of the primary targets of LPS action during sepsis. In earlier studies we have described HA-1A-induced immune adherence of LPS to complement receptors on erythrocytes, and showed that pre-incubation with HA-1A, in the presence of complement and red blood cells, markedly reduced LPS-induced cytokine production from peripheral blood mononuclear cells. In the present study, we measured the effect of immune adherence of LPS in the presence of HA-1A on the responses of cultured endothelial cells, and found that subsequent expression of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and secretion of the cytokines interleukin-6 and granulocyte-macrophage colony stimulating factor were markedly reduced. Moreover, the ability of LPS to increase levels of tissue factor procoagulant activity on endothelial cells was markedly diminished by LPS immune adherence to HA-1A. This decrease in endothelial activation in response to LPS following immune adherence to HA-1A may play a significant role in the protective effect of HA-1A in vivo during the course of Gram negative sepsis.
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PMID:Antilipid A monoclonal antibody HA-1A decreases the capacity of bacterial lipopolysaccharide to activate human vascular endothelial cells by an immune adherence mechanism. 751 52

Small numbers of CD34+ primitive hematopoietic progenitors are found in normal human peripheral blood. These cells differentiate to myeloid or lymphoid lineage under the influence of different growth factors. We investigated the effects of IL5 and other growth factors on the production of eosinophils from peripheral blood CD34+ cells. CD34+ cells were enriched from normal donors by apheresis and positive selection using an affinity column and plated in agarose with different combinations of cytokines. At 14 days of growth a triple stain technique was used to identify eosinophil, monocyte, and neutrophil colonies. IL5 alone did not support colony growth from CD34+ cells. In contrast, GM-CSF and IL3 alone or together without added IL5 supported the generation of more than 50% pure eosinophil colonies. Addition of IL5 did not change the total number of colonies, but increased the fraction of pure eosinophil colonies to over 70%. Addition of G-CSF reduced the percentage of eosinophil colonies and increased the percentage of neutrophil colonies. Under the best conditions for eosinophil colony growth (IL3+GM-CSF+IL5), the addition of interferon-alpha or bacterial lipopolysaccharide inhibited colony growth by 51 and 58%, respectively. Addition of interferon-gamma, tumor necrosis factor-alpha, or dexamethasone had no effect on eosinophil colonies. Since IL5 alone did not support colony growth from CD34+ cells, we determined when IL5-responsive cells appeared in culture. Cells were grown initially with IL3 + GM-CSF in suspension, washed, and plated in agarose with IL5 alone. Only when progenitors were grown at least 3 days could IL5 serve as the single growth factor supporting pure eosinophil colony growth (47 colonies/10(4) cells plated at Day 3 and 134 colonies/10(4) cells at Day 7). We used neutralizing anti-IL5 antibodies to demonstrate that this late acting IL5 growth effect was specific, and that differentiation of eosinophils in the presence of IL3 + GM-CSF was IL5 independent. Using reverse-transcriptase polymerase chain reaction, the mRNA encoding the eosinophil-specific protein eosinophil peroxidase (EPO) was not detected in Day 0 CD34+ cells, but was demonstrated by Day 3 of culture. We conclude that within 3 days of culture, peripheral blood CD34+ cells can become committed to the eosinophil lineage as demonstrated by responsiveness to IL5 and production of EPO transcripts.
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PMID:Modulation of growth and differentiation of eosinophils from human peripheral blood CD34+ cells by IL5 and other growth factors. 753 Nov 18

An injection of Escherichia coli lipopolysaccharide (LPS) increased the activity of histidine decarboxylase (HDC) in bone marrow (BM) cells of C3H/HeN mice much more than in C3H/HeJ mice, which are resistant to various effects of LPS. In WBB6/F1 (W/Wv) mice, which are genetically deficient in mast cells, HDC activity increased more than in C3H/HeN mice. Cultured BM cells of W/Wv mice spontaneously synthesized histamine in a HDC-dependent way. LPS caused a slight increase in HDC-associated histamine synthesis by these cells. Treatment of the BM cells with murine recombinant granulocyte-macrophage colony stimulating factor (mrGM-CSF) increased the histamine synthesis. In addition, treatment with mrGM-CSF made the cells respond to LPS by a dose-dependent increase in HDC activity and histamine synthesis. Most dish-adherent BM cells that had been treated with both mrGM-CSF and LPS for 48 h were stained for nonspecific esterase and not for chloroacetate esterase, and had twice as much HDC activity as the nonadherent cells had. Immunocytochemical analysis of the BM cells of W/Wv mice treated with both mrGM-CSF and LPS showed that HDC was in the cytoplasm of cells having Mac-1, a macrophage-differentiation antigen. These results suggest that cells of the macrophage lineage in the BM of mice synthesize histamine.
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PMID:Histamine synthesis by cells of the macrophage lineage in bone marrow of mice. 754 1

The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is well established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability. 757 80

The high-affinity receptors for interleukin-3 (IL-3), GM-CSF, and IL-5 are composed of a ligand binding (alpha-) and a transducing (beta-) subunit. Two distinct transducing subunits (clones AIC2A and AIC2B) have been cloned from mouse, whereas in humans, only one (common) beta-subunit (beta c) has been found. A PCR-based cloning strategy was used to obtain a full-length cDNA sequence from rat microglia including 5'-untranslated regions. Sequence analysis revealed a number of features indicative of the presence of only one beta-subunit in the rat. Most likely, the new rIL-3R beta cDNA is the rat equivalent of human respective murine (AIC2B) beta c subunits. Regulation of rIL-3R beta mRNA expression was investigated in cultured microglia and in vivo. Purified microglia expressed significant amounts of rIL-3R beta mRNA. Addition of lipopolysaccharide (LPS) resulted in a marked upregulation of rIL-3R beta mRNA within approximately 4 hr. No downregulation was observed within 1 week's treatment. No rIL-3R beta mRNA was detectable in normal rat brain. However, 3 hr after a single injection of LPS into the tail vein of a rat, a marked induction of receptor mRNA occurred in a variety of brain regions. Transcriptional rates subsided significantly after 24 hr. rIL-3R beta mRNA was visualized by in situ hybridizations with cRNA antisense probes in ramified cells formerly characterized as microglial cells. rIL-3R beta mRNA was also induced in rat brain after occlusion of middle cerebral artery (MCAO).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cloning of rat interleukin-3 receptor beta-subunit from cultured microglia and its mRNA expression in vivo. 764 20

We hypothesized that therapy with granulocyte-macrophage colony stimulating factor (GM-CSF) would decrease intensity of murine Pneumocystis carinii pneumonia by upregulating alveolar macrophage function. Mice were depleted of CD4+ T lymphocytes and then inoculated intratracheally with P. carinii. Four weeks later, they received recombinant murine GM-CSF (rmGM-CSF) 5 micrograms/d subcutaneously for 7 and 14 d. At the end of therapy lung tissue was scored for intensity of P. carinii infection by silver methenamine stain and for inflammation by hematoxylin-eosin stain. We found that rmGM-CSF therapy significant decreased the intensity scores of PCP infection in comparison to control mice (1.88 +/- 0.47 vs 3.06 +/- 0.12, p < 0.001). Inflammation scores were not significantly different in the rmGM-CSF group compared with the control group (1.83 +/- 0.47 vs 2.83 +/- 0.67). Alveolar macrophages from mice treated with rmGM-CSF released significantly more tumor necrosis factor-alpha (TNF-alpha) than cells from control mice after in vitro stimulation with lipopolysaccharide (LPS) alone (2.65 +/- 0.30 vs 1.45 +/- 0.26 ng/ml, p = 0.01) or with LPS plus murine recombinant interferon-gamma (4.16 +/- 0.51 vs 2.25 +/- 0.34 ng/ml, p = 0.01). We conclude that GM-CSF therapy reduces the intensity of PCP and this effect is associated with an enhanced alveolar macrophage TNF-alpha production.
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PMID:Granulocyte-macrophage colony stimulating factor and Pneumocystis carinii pneumonia in mice. 769 58

There is an antigen presenting cell (APC) in the lymphoid organs capable of presenting exogenous antigen (Ag) with major histocompatibility complex (MHC) class I molecules. This study was initiated to isolate clones of these APC to definitively establish their phenotype and to further study their properties. Murine bone marrow macrophages (BM M psi) were immortalized by overexpression myc and raf oncogenes. Five BM M psi cell lines were generated that are phagocytic and expressed at their surface M psi differentiation Ag. All five cell lines processed and presented exogenous ovalbumin (OVA) with MHC class I molecules. They all presented OVA-linked to a phagocytic substrate 10(2)-10(4)-fold more efficiently than soluble Ag. Clonal isolates of two of the M psi cell lines had an identical phenotype and functional properties as the uncloned lines. These results definitively establish that M psi are APC with the capacity of presenting exogenous Ag with MHC class I molecules. Interferon (IFN)-gamma interleukin-4, granulocyte-macrophage colony stimulating factor and lipopolysaccharide either alone or in combination induced little or no augmentation and in some cases decreased presentation of exogenous OVA with MHC class I. In contrast, all of M psi activating factors increased MHC class I expression. Moreover, IFN-gamma increased the presentation of cytosolic OVA, demonstrating differences between the presentation of cytosolic Ag versus exogenous Ag with MHC class I. Finally, some lines constitutively processed and presented exogenous OVA with MHC class II while others only presented after stimulation with IFN-gamma. These results demonstrate that the pathways involved in the presentation of exogenous Ag with MHC class I and class II are independently regulated and that a cloned cell is capable of presenting exogenous Ag through both pathways.
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PMID:Presentation of exogenous antigens by macrophages: analysis of major histocompatibility complex class I and II presentation and regulation by cytokines. 792 70

The immunomodulating action of Neisseria meningitidis lipopolysaccharide (LPS) incorporated into liposomes and the activation of different populations of immunocompetent cells or the secretion of cytokines were studied. LPS stimulated an anti-sheep red blood cell (SRBC) plaque-forming cell response in the spleen of mice after simultaneous injection of LPS and SRBC but if LPS was administered 3 days before the immunization with SRBC the response to SRBC was strongly suppressed. After the incorporation of LPS into liposomes the stimulation index was increased from 6 to 19 and the liposomal LPS did not suppress the immune response to SRBC. The incorporation of LPS into liposomes leads to enhancement of B-mitogenic properties of LPS, as liposomal LPS stimulated the proliferation of splenocytes in mice better than free LPS and has no influence on the thymocytes. The liposomal LPS induced more prolonged and significant accumulation of IgM-secreting cells in the spleen of mice in comparison with the free LPS. Liposomal LPS also induced more active accumulation of IFN-gamma in human peripheral blood mononuclear cells and less active accumulation of monokines, contributing to the realization of the toxic properties of endotoxin (IL-1 alpha, TNF-alpha, IL-6 and GM-CSF). These results demonstrated that the incorporation of N. meningitidis LPS into liposomes dramatically changed its immunomodulating activity. The data obtained are important for the construction of an adjuvant formulation for synthetic immunogens capable of inducing genetically unrestricted immune responses.
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PMID:Non-specific modulation of the immune response with liposomal meningococcal lipopolysaccharide: role of different cells and cytokines. 799 14

Partial resorption or abortion (depending upon the stage of gestation) can be induced with lower doses of lipopolysaccharide (LPS) (DIFCO) and human R-TNF than previously demonstrated. As can be expected, the abortion-prone CBA x DBA/2 and B10 x B10.A mating combinations are the most sensitive to such low doses. LPS synergizes with low doses of IL-2, gamma interferon, poly(I).poly(C) 12U. Treatment by GM-CSF, IL-3, or anti-natural killer antiserum decreases both TNF levels and abortion rates. Similar prevention of induced resorptions are obtained with either a neutralizing polyclonal rabbit anti-TNF antiserum or with pentoxyfilline, which has been shown to reduce resorption rates in CBA x DBA/2 pregnancies. More important, abortions induced by low doses of LPS or R-TNF can be prevented by alloimmunization. During late gestation, on the contrary, LPS- or TNF-induced delivery cannot be counteracted by alloimmunization nor by a progesterone-induced blocking factor, at least in the regimens employed by us. Therefore, although resorptions and parturition share common pathways consisting of immune mediators, they are not regulated similarly by the maternal immune system.
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PMID:Synergy of lipopolysaccharide and inflammatory cytokines in murine pregnancy: alloimmunization prevents abortion but does not affect the induction of preterm delivery. 806 21

The acquisition of a bactericidal activity by the cellular immune system is one of the mechanisms of prime importance for the development of the cellular resistance to infection. It involves the specific recognition of the pathogenic microorganism associated with the direct or indirect activation of effector cells. The in vivo type of replication of the infectious microorganism provides the adaptive response of the host. This response differs according to extracellular or intracellular multiplying microorganism. The acquired resistance to extracellular multiplying bacteria (ie, capsulated bacteria) is linked to the B cell production of specific antibodies that are associated with the activated complement fragments, that enable bacterial opsonization, activation and recruiting of polymorphonuclear phagocytes. These cells did acquired a greater capacity to ingest and to kill bacteria at sites of infection. Such phenomenon could be also associated with acute purulent necrotizing lesions. On the other hand, intracellular multiplying bacteria are mostly associated with chronic granulomatous non pyogenic lesions, and such bacteria are also able to survive and to replicate into the non activated professional mononuclear phagocytes. The acquired resistance against such bacteria is linked to the occurrence of a non specific bactericidal capacity of macrophages, that inhibit and/or kill replicative intracellular microorganisms. Such macrophage bactericidal capacity is dependent upon the gradual and stepwise cellular activation provided by several extracellular and membrane associated signals. Sequential signals are produced by the specific recognition of committed T CD4+ lymphocytes mediated by the infected macrophages through the MHC class 2 restriction of the peptide presentation. One of the major signal of cellular communication to induce macrophage priming involves the production of Interferon gamma (IFN gamma). Secondary signals are needed to induced full macrophage activation defined by phenotypic, metabolic and functional alterations which include their acquired increase capacity to kill intracellular bacteria and tumor cells. Secondary signals involve the production of cytokines such as TNF alpha, IL2 and GM-CSF being transduced by bacterial cell wall products (such as lipopolysaccharide, teichoic acid, or lipoarabinomanan) or by the calcitriol pathway recently described during mycobacterial infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Bactericidal activity of cells of the immune system]. 812 21

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