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)

Major histocompatibility complex (MHC) class II molecules can present peptides derived from two different sources. The predominant source of peptide in uninfected antigen presenting cells (APCs) is from self-proteins that are synthesized within the cell and traffic through the MHC class II compartment. The other source of antigen is endocytosed proteins, which includes both self- and foreign proteins. Foreign protein antigens generate adaptive immune responses, whereas self-peptides stabilize the MHC class II heterodimer on the cell surface, allowing positive and negative selection of thymocytes. Therefore, self-antigens play an important normal role in shaping the T cell receptor repertoire as well as a pathological role in autoimmunity. To determine whether processing and presentation of self-antigens by MHC class II molecules differs depending on whether the antigen is supplied through synthesis within the cell or by endocytosis, we used a T cell clone against an Ealpha peptide presented by I-Ab to show that processing through these two routes can differ. We also show that mice can be tolerant to the epitope formed through the endogenous route, but responsive to the epitope that can be formed through endocytosis. This suggests that negative selection occurs primarily against antigens that are synthesized within the APC, and that endocytosed self-antigens could serve as autoantigens. Finally, we also demonstrate that lipopolysaccharide-activated B cells are defective for uptake, processing, and presentation of this self-antigen, and that this correlates with the increased expression of the costimulatory molecules B7.1 and B7.2. This may provide a model for studying the onset of an autoimmune response.
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PMID:Exogenously provided peptides of a self-antigen can be processed into forms that are recognized by self-T cells. 956 33

Recent studies have indicated that glial cells such as astrocytes and microglia are activated in an early and delayed episode after brain damage. However, the mechanism and function of glial activation are still unclear. I examined whether the induction of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1) and major histocompatibility complex (MHC) antigen was involved in the glial activation. The microinjection of interferon-gamma and lipopolysaccharide into rat hippocampus induced MHC class II and iNOS in microglia. The iNOS induction may be involved in the activation of tyrosine kinases and transcription factors such as signal transducer and activator of transcription-1 (STAT1) and nuclear factor-kappa B (NF-kappa B). Subsequently, neuronal cell death occurred in the hippocampus, but cell death was undetectable in both microglia and astrocytes that expressed HO-1. Thus, induction of iNOS and HO-1 in glial cells may be involved in hippocampal neurodegeneration and resistance to oxidative stress in glial cells, respectively. In Alzheimer's disease (AD) brains, iNOS expression was at a very low level, although STAT1 and NF-kappa B were significantly increased. Also, Bcl-2, Bcl-x, Bak, Bad and p53 were increased in AD brains. These observations suggest that oxidative stress and glial activation without iNOS induction may be involved in neurodegeneration of AD brains.
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PMID:[Functional activation of glial cells in early and delayed episodes of the brain damage]. 958 78

The bovine leukaemia virus (BLV) is a retrovirus that infects mainly B lymphocytes of cattle, but proviral DNA can also be isolated from monocytes/macrophages. This study investigated the effect of BLV infection on surface antigens on freshly isolated peripheral blood monocytes and cultured monocyte-derived macrophages, with and without lipopolysaccharide (LPS) stimulation. The effect of BLV infection on phagocytic activity of CD14+ monocytes was also assessed. The percentage of monocytes expressing the surface antigens CD11b, CD32 (FcgammaRII), MHC class II and the surface antigen recognised by mAb DH59B were increased in BLV-positive cattle. In contrast, expression intensity of all markers was low in samples from BLV-positive cattle. CD14+ monocytes from BLV-positive cattle showed less Fcgamma-receptor-mediated phagocytosis compared to monocytes from BLV-negative cattle. After 7 days in culture, there was evidence for shedding/downregulation of surface antigens on monocyte-derived macrophages, in particular on cells from BLV-positive cattle. LPS stimulation decreased the percentage of cells expressing the measured markers in monocyte-derived macrophages taken from BLV-negative cattle, but not in cultures derived from BLV-positive cattle. The results provide further evidence for an altered function of monocytes and macrophages in BLV-infected cattle.
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PMID:Analysis of the phenotype and phagocytic activity of monocytes/macrophages from cattle infected with the bovine leukaemia virus. 964 53

Bacterial DNA and immunostimulatory (i.s.) synthetic CpG-oligodeoxynucleotides (ODN) act as adjuvants for Th1 responses and cytotoxic T cell responses to proteinaceous antigens. Dendritic cells (DC) can be referred to as "nature's adjuvant" since they display the unique capacity to sensitize naive T cells. Here, we demonstrate that bacterial DNA or i.s. CpG-ODN cause simultaneous maturation of immature DC and activation of mature DC to produce cytokines. These events are associated with the acquisition of professional antigen-presenting cell (APC) function. Unfractionated murine bone marrow-derived DC and FACS-fractionated MHC class IIlow (termed immature DC) or MHC class IIhigh populations (termed mature DC) were stimulated with bacterial DNA or i.s. CpG-ODN. Similar to lipopolysaccharide, i.s. CpG-ODN caused up-regulation of MHC class II, CD40 and CD86, but not CD80 on immature and mature DC. In parallel both DC subsets were activated to produce large amounts of IL-12, IL-6 and TNF-alpha. CpG-ODN-activated DC displayed professional APC function in allogeneic mixed lymphocyte reaction and in staphylococcal enterotoxin B-driven naive T cell responses. We interpret these findings to mean that bacterial DNA and i.s. CpG-ODN cause maturation (first step) and activation (second step) of DC to bring about conversion of immature DC into professional APC.
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PMID:Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. 964 86

The hormonal active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1, 25(OH)2D3), inhibits (through an unknown mechanism) the ability of monocytes/macrophages to induce T-cell activation. For T cells to be optimally activated, recognition of antigen/major histocompatibility complexes (MHC) by the T-cell receptor (TCR) must be accompanied by a second costimulatory signal. Considerable experimental data now suggest that this costimulatory signal is predominantly generated by B7.1 and/or B7.2 molecules, expressed on antigen-presenting cells (APC), when engaged to their counter-receptor, CD28, present on T cells. To determine whether the inhibitory effect of 1,25(OH)2D3 on monocytes/macrophages might involve modulation of the expression of B7.1 and B7.2 molecules, we analysed (by flow cytometry) the influence of 1,25(OH)2D3 and an analogue, KH 1060, on the expression of these two molecules at the surface of resting human peripheral blood monocytes. In parallel, we tested the effect of these two agents on human monocyte expression of cell-surface markers (CD14 and CD4) and antigen-presenting molecules (MHC class I and MHC class II). Our results showed that both 1,25(OH)2D3 and KH 1060 inhibited the basal expression of B7.2 in a dose- and time-dependent manner, without affecting B7.1. Moreover, these two compounds increased CD14 and reduced MHC class II and CD4 expression. Furthermore, the effect of 1,25(OH)2D3 on B7 molecule expression in combination with lipopolysaccharide (LPS) or cytokines, including interleukin-10 (IL-10), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), was studied. The 1,25(OH)2D3-induced B7.2 down-regulation was still detectable when monocytes were activated by IL-10, IFN-gamma and TNF-alpha but not with LPS. Moreover, the induction of B7.1 by TNF-alpha was inhibited by addition of 1, 25(OH)2D3. We conclude that the ability of 1,25(OH)2D3 to decrease B7.2 expression on human monocytes might contribute to its inhibitory effect on APC-dependent T-cell activation and to its immunosuppressive properties observed in autoimmune diseases and organ transplantation.
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PMID:Vitamin D differentially regulates B7.1 and B7.2 expression on human peripheral blood monocytes. 982 86

To investigate the adjuvant effect of intestinal flora on macrophage-colony-stimulating factor-responsive macrophage progenitors from spleen and bone marrow, we compared progenitor numbers and phenotypic characteristics of in vitro matured macrophages in germ-free and flora-associated mice (conventional, Escherichia coli-monoassociated and conventionalized mice). The data obtained show that the flora affected differentially bone marrow and spleen progenitors. It increased the numbers of progenitors in the spleen but not in the bone marrow. It did not modify the expression of F4/80, Mac-1 and major histocompatibility complex (MHC) class II on bone-marrow-derived macrophages (BMDM), while it clearly up-regulated MHC class II expression on spleen-derived macrophages (SDM). This effect was more pronounced in flora-associated ex germ-free mice than in conventional mice and it was greatly enhanced in the absence of M-CSF. In vitro stimulation by lipopolysaccharide had no effect on marker expression of BMDM, while it decreased F4/80 and enhanced MHC class II molecules on SDM from germ-free and flora-associated mice. However, the expression of MHC class II remained lower in germ-free mice. Enhancement of MHC class II molecule expression on SDM may contribute to the protective role of flora, because successful immune responses are dependent on the expression of these molecules.
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PMID:Influence of intestinal microflora on murine bone marrow and spleen macrophage precursors. 987 92

To investigate the early events of Helicobacter pylori infection in a mouse model, CD1 mice were infected with a type I (CagA+/VacA+) H. pylori strain. Up to 4 weeks after infection the majority of gastric tissue biopsies were positive in culture. Immunohistochemical analysis showed that inflammatory changes started to occur after 3 weeks. Four weeks after infection a significant increase in T cells was observed in the cardia/corpus region of the stomachs of infected mice. These T cells were CD4+ and CD8+, and they were located in an area with increased expression of MHC class II antigens. In 50% of the infected mice also an increased number of mast cells was seen. Furthermore, aggregates of B and T cells were present in the submucosa. Characterization of cytokines by immunohistochemistry showed an increase in IL-5-secreting cells in the inflamed area of the infected stomach. No difference was observed between interferon-gamma (IFN-gamma)-, IL-4- and IL-10-secreting cells in control and infected mice. These results suggest that no polarized T-helper cell response was present at this early phase of infection. Infection with H. pylori also induced a serum response and especially IgG was increased after 4 weeks of infection. However, no particular increase in IgG1, IgG2a or IgG3 isotype was observed. Part of the serum antibodies was directed against lipopolysaccharide (LPS), but no evidence for anti-Lewis antibodies or antibodies against epitopes on the gastric mucosa was found.
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PMID:The inflammatory response in CD1 mice shortly after infection with a CagA+/VacA+ Helicobacter pylori strain. 1019 13

Multiple sclerosis (MS) is a central nervous disease thought to be elicited by an autoimmune process. Many studies in recent years have concentrated on finding the alterations in the peripheral blood immune profile in MS patients that would reflect disease activity. In the present study, we investigated surface antigen expression on lymphocytes and granulocytes from MS patients and control subjects. We have studied 29 patients suffering from relapsing-remitting or relapsing-progressive forms of MS. The disease was diagnosed in all patients at least 12 months before inclusion into the study. All patients had no attack at the study entry date or within a previous month. The control group included 29 age-matched subjects. Phenotyping of peripheral blood leukocytes was carried out with different fluorescence-conjugated murine monoclonal antibodies. The analysis was performed with three-color flow cytometry. The following antigens were determined [cluster of definition (CD)]: leukocyte common antigen (LCA) (B220, T 200, Ly-5), CD45; LPS-R (lipopolysaccharide receptor), CD14; found on all T cells, CD3; LFA-2 (lymphocyte function associated antigen, T 11), CD2; coreceptor for MHC class II molecules, found on helper T cells, CD4; coreceptor for MHC class I molecules, found on suppressor/cytotoxic T cells, CD8; B4, found on all human B cells, CD19; NCAM (neural cell adhesion molecule), CD56; integrin beta2 subunit, associated with CD11a (CD11a/CD18, LFA-1, alphaLbeta2) and CD11b (CD11b/CD18, Mac-1,CR3, alphaMbeta2), CD18; alphaL, alpha subunit of integrin LFA-1 (alphaLbeta2, CD11a/CD18), CD11a; alphaM, alpha subunit of integrin Mac-1 (CR3, alphaMbeta2, CD11b/CD18), CD11b; ICAM-1 (intercellular adhesion molecule), CD54; H-CAM, Hermes antigen, Pgp-1, CD44; AIM (activation inducer molecule), early activation antigen, CD69; T-cell receptor gammadelta, TCR gammadelta. In the MS group, we have found a significant increased expression of CD54 and CD44 antigens on lymphocytes, and higher percentage CD54(+) and CD11a+CD54(+) lymphocytes out of all lymphocytes compared with the control group. We have also found a significant increased expression of CD11a, CD18 and CD54 antigens on granulocytes, and higher percentage CD11b+CD18(+) granulocytes out of all granulocytes in MS patients compared with control. Higher levels of expression of the adhesion molecules may reflect the activation state of leukocytes in MS patients.
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PMID:Phenotyping analysis of peripheral blood leukocytes in patients with multiple sclerosis. 1021 Sep 17

IgG molecules can be highly tolerogenic carriers for associated antigens. Previously, we reported that recipients of bone marrow or lipopolysaccharide-stimulated B-cell blasts, both of which were retrovirally gene-transferred with an immunodominant peptide in-frame with the variable region of a murine IgG heavy chain, were rendered profoundly unresponsive to that epitope. To further investigate whether tolerance to larger molecules can be achieved via this approach and whether the IgG scaffold is important for induction and maintenance of immunological tolerance, we engineered two retroviral constructs encoding the cI lambda repressor (MBAE-1-102 and MBAE-1-102-IgG) for gene transfer. Our results show that recipients of bone marrow or peripheral B cells, transduced with the MBAE-1-102-IgG recombinant, are hyporesponsive to p1-102. In addition, the self-IgG scaffold enhanced the induction and maintenance of such an immune hyporesponsiveness. Thus, our studies demonstrate that in vivo-expressed IgG heavy chain fusion protein can be processed and presented on the appropriate MHC class II, resulting in hyporesponsiveness to that antigen and offering an additional therapeutic approach to autoimmune diseases.
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PMID:Induction of hyporesponsiveness to intact foreign protein via retroviral-mediated gene expression: the IgG scaffold is important for induction and maintenance of immune hyporesponsiveness. 1041 23

The primary IL-13 receptor complex on human monocytes is believed to be a heterodimer comprised of the IL-4R alpha chain and the IL-2R gamma chain (gamma(c))-like molecule, IL-13R alpha1. mRNA levels for IL-13R alpha1, but not IL-4R alpha, were markedly decreased in in vitro monocyte-derived macrophages (MDMac), and with increasing time of monocytes in culture correlated with the loss of IL-13 regulation of lipopolysaccharide-induced TNF-alpha production. Analysis of cell lines Daudi and THP-1 that differentially express gamma(c) and IL-13R alpha1 showed that IL-13 can activate STAT6 in IL-13R alpha1-positive THP-1 cells but not in gamma(c)-positive, IL-13R alpha1-negative Daudi cells. IL-13 activation of STAT6 was reduced in MDMac which was associated with diminished IL-13-induced expression of CD23 and MHC class II. However, with reduced IL-13R alpha1 expression and low nuclear STAT6 activity, some IL-13-induced responses were unaltered in magnitude in MDMac. In the absence of functional IL-13R alpha1 and gamma(c), IL-13 must signal through an alternative receptor complex on MDMac. Experiments with a blocking antibody to IL-4R alpha showed that this chain remains an essential component of the IL-13 receptor complex on MDMac.
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PMID:Diminished responses to IL-13 by human monocytes differentiated in vitro: role of the IL-13Ralpha1 chain and STAT6. 1042 71


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