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)

To better define the regulation and expression of bovine major histocompatibility complex (MHC) antigens, the bovine B lymphoblastoid cell line, BL3, was exposed to gamma-irradiation and surviving cells were immunoselected for MHC class I antigen loss. The resulting class I expression loss variant, BL3.1, was characterized at both the protein and genetic levels to ascertain the nature of the defect. Microfluorimetry analysis revealed a 3--5-fold surface density reduction of all class I products on BL3.1 cells relative to the parental BL3 cells. This decreased surface expression was specific for MHC class I and not for MHC class II or the non-MHC-linked gene product, immunoglobulin (Ig). Northern and quantitative slot blot analyses demonstrated a corresponding diminution of class I RNA in BL3.1 suggesting a transcriptional level defect. Nuclear run-off and transcription inhibition experiments confirmed no post-transcriptional changes while Southern blot analysis provided no evidence for alterations within or near the class I genes. To help elucidate the mechanism of altered class I expression, the parent, BL3, and variant, BL3.1, were cultured with factors known to enhance MHC class I transcription. Interferon (IFN)-gamma, lipopolysaccharide (LPS), and activated peripheral blood lymphocyte (PBL) supernatant cultured with both cell lines induced MHC class I transcription and surface expression 2--3-fold greater than the untreated controls. It is likely, therefore, that a genetic alteration outside of the class I genes has occurred within BL3.1 impairing expression of MHC class I.
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PMID:Impairment of MHC class I transcription in a mutant bovine B cell line. 134 4

We have investigated the ability of various antigen-presenting cell (APC) types to induce primary anti-viral cytotoxic T lymphocyte (CTL) responses by single in vitro stimulation. Of these APC types, only dendritic cells (DC) and RMA-S lymphoma cells could induce primary CTL responses, but by divergent mechanisms. DC were capable of generating primary virus-specific CTL, either by presenting viral peptide or processed infectious virus. In contrast, RMA-S cells could not present endogenous antigen, e.g. after virus infection, but this cell line very efficiently presented exogenous viral peptides to induce primary virus-specific CTL in vitro. Spleen cells, lipopolysaccharide-induced B cell blasts or the non-mutated RMA cells did not have the ability to trigger unprimed T cells by single in vitro stimulation. We have investigated several characteristics important for primary CTL response induction by DC and RMA-S cells (summarized in Fig. 6). Primary CTL response induction by DC or RMA-S cells was blocked by anti-LFA-1 or anti-CD8 monoclonal antibodies (mAb). DC rapidly aggregated with unprimed T cells, which was independent of LFA-1 and CD8 molecules. RMA-S cells did not form conjugates with unprimed T cells. Despite their abundant major histocompatibility complex (MHC) class I cell-surface expression, DC did not bind much exogenously added viral peptide. In contrast, the MHC class I molecules on RMA-S cells bound a large quantity of exogenously administered peptide. Powerful adhesion by DC and high expression of relevant MHC/peptide complexes on RMA-S cells are important features in the initial contact with unprimed T lymphocytes. In a later stage of contact, both DC and RMA-S cells activate LFA-1 (and CD8) molecules at the T cell surface to strengthen and maintain the contact between T cell and APC.
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PMID:Mechanisms of induction of primary virus-specific cytotoxic T lymphocyte responses. 142 25

Regulation of ovine alveolar macrophage function by recombinant interferon gamma (rIFN gamma) and lipopolysaccharide (LPS) was investigated. Ten units per millilitre of rIFN gamma increased surface expression of MHC class I and class II (DR alpha, DP alpha, and DQ alpha) molecules but not other surface antigens examined. The upregulation of MHC class II expression was specifically blocked by rIFN gamma specific monoclonal antibodies and determination of a dose/response curve established that the minimum concentration of rIFN gamma required for increased class II expression was 0.1 U ml-1 and for increased class I expression, 1 U ml-1. Northern blot analysis indicated that rIFN gamma mediated increases in surface MHC class I and class II expression were due to increased levels of specific mRNA. Using Northern blot analysis and homologous human cDNA probes we failed to detect mRNA encoding the cytokines IL-1 alpha, IL-1 beta, and TNF alpha in RNA extracted from freshly isolated macrophages or macrophages cultured in medium alone. Exposure of macrophages to LPS increased production of all three cytokines although kinetics of upregulation varied. TNF alpha mRNA was induced to maximal levels within 1 h, declining thereafter. IL-1 alpha mRNA was detected at 1 h post stimulation with a maximal level at 5 h, but none at 24 h. In contrast, IL-1 beta mRNA was not detected until 5 h after stimulation with a low level remaining at 24 h. Dose response analysis indicated that LPS concentrations of 100 pg ml-1 induced detectable levels of TNF alpha mRNA while levels as low as 10 pg ml-1 induced secretion of bioactive IL-1. Analysis of the kinetics of secretion of bioactive IL-1 from LPS stimulated macrophages indicated that levels peaked at 24 h post stimulation.
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PMID:Characterisation of ovine alveolar macrophages: regulation of surface antigen expression and cytokine production. 157 Jun 84

Interactions between leukocytes and endothelial cells, particularly in the microvasculature, are important for the initiation and regulation of tissue inflammation. These interactions are regulated by the recognition of specific cell adhesion molecules (CAM) on both leukocytes and endothelial cells. In this study, we examined the modulation of cell surface expression of MHC antigens and the CAM intercellular adhesion molecule 1 (ICAM-1), lymphocyte function antigen 3 (LFA-3), and CD44 on human dermal microvascular endothelial cells (HDMEC) both grown in monolayers and differentiated into capillary-like structures on the basement membrane-like substrate matrigel. HDMEC grown in monolayers or differentiated on matrigel express comparable cell surface MHC class I, LFA-3, CD44, and ICAM-1. ICAM-1, but not LFA-3 or CD44, was increased in expression in a dose- and time-dependent manner by interleukin 1 (IL-1) alpha, tumor necrosis factor (TNF) alpha, lipopolysaccharide (LPS), or interferon (IFN) gamma. Comparable upregulation was observed both in cells grown in monolayers and cells differentiated on matrigel. IL-1 alpha, TNF alpha, and LPS increased ICAM-1 expression on average 100-200% whereas IFN gamma was somewhat less potent. Comparative studies with human umbilical vein endothelial cells (HUVEC) demonstrated consistently lower levels of ICAM-1 expression on HUVEC, but greater increases after cytokine stimulation. Pretreatment with dexamethasone or transforming growth factor (TGF) beta did not affect baseline expression of ICAM-1 or inhibit upregulation of ICAM-1 on HDMEC by IL-1 alpha, TNF alpha, LPS, or IFN gamma. Both IFN gamma and TNF alpha, but not IL-1 alpha increased MHC class I expression, whereas only IFN gamma induced the expression of HLA-DR on HDMEC. The effect of IL-1 alpha, TNF alpha, or IFN gamma was inhibited by antibody to the specific cytokine, but was unaffected by antibody to other cytokines. Additionally, IFN alpha or beta inhibited upregulation of HLA-DR by IFN gamma, but had no effect on the increased MHC class I or ICAM-1 expression mediated by this cytokine. These data demonstrate that the expression of CAM and MHC antigens on small vessel-derived endothelial cells is different from that observed on large-vessel HUVEC, is regulated by the presence of multiple cytokines operating via distinct pathways, and the expression and regulation of these proteins appear to be similar on cells that have been grown in monolayers to those morphologically differentiated into blood vessel-like structures.
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PMID:Studies of the modulation of MHC antigen and cell adhesion molecule expression on human dermal microvascular endothelial cells. 190 7

Immunomodulation of rodent islets can significantly prolong allograft survival. We utilized a murine model of primary islet transplantation to study the relationship between allograft survival and the quantitative pretransplant expression of class I and II MHC antigens in freshly isolated CBA/J islets, and islets subjected to 37 degrees C tissue culture, brief culture at 7 degrees C, or exposure of the donor to lipopolysaccharide. Seven-day culture resulted in decreased class II expression, a tendency to decreased class I expression, and a significant prolongation of allograft survival. Brief culture at 7 degrees C resulted in increased class I expression, a trend to decreased class II expression, and no significant change in allograft survival. Donor pretreatment with LPS resulted in increased class I expression without significant change in class II expression and was correlated with prolongation of allograft survival. These studies demonstrate that an upregulation of MHC class I by in vitro or in vivo islet pretreatment is not associated with an acceleration of islet rejection. Reduction of class II was associated with delayed rejection. These results do not support a major role of the indirect pathway of antigen presentation in islet rejection in vivo. Certain protocols that alter the usual expression of class I and II on pancreatic islets are associated with alteration in the initiation and/or propagation of the normal cell-mediated rejection process, suggesting that the concept of pretransplant treatment should continue to be pursued.
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PMID:Major histocompatibility complex antigens and murine islet allograft survival. 198 95

We studied functional and immunohistochemical characteristics of cultured rat microglia. Unstimulated microglia did not proliferate. Microglia stimulated with LCM (L929 conditioned medium: colony stimulating factor-1) had proliferative activity and increased acid phosphatase activity. LPS (lipopolysaccharide) and IFN gamma (interferon-gamma) but did not affect proliferative activity. Immunohistochemically, RCA-1 lectin and GS-1 lectin, which react to beta-D-galactose and alpha-D-galactose respectively, strongly reacted to the cytoplasm and membrane of unstimulated microglia. After stimulation with LCM, microglia elongated processes and decreased response to these lectins. On the other hand, microglia stimulated with LCM showed increased reactivity to monoclonal antibody of vimentin. Microglia stimulated with LPS had round shape and had response to these lectins and vimentin. Microglia stimulated with IFN gamma had adhesive activity and weakly stained with these lectins but not with vimentin. ED-1 (monoclonal antibody of rat monocytes/macrophages) reacted to unstimulated and stimulated microglia. In flow cytometry, unstimulated microglia expressed OX-18 (MHC class I) and W3/25 (CD4) antigen. After stimulation with IFN gamma, microglia were induced to express these antigens. CD4 antigen is a marker of helper/inducer T cells and thought to be a receptor of HIV. The results that microglia had CD4 antigen which was further induced with IFN gamma are important to investigate infection of the CNS with HIV. OX-6 (Ia) antigen was induced with IFN gamma. This indicates that the microglia plays a central role in the CNS immune reaction. These characteristics of cultured rat microglia provide useful informations to investigate the pathogenesis of the CNS disorders.
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PMID:[Functional and immunohistochemical studies of cultured rat microglia]. 206 Feb 34

Two class I major histocompatibility (MHC) mutant mouse strains, H-2bm14 and H-2bm6, differ from the strain of origin C57BL/6 (B6, H-2b) in one and two amino acids of the H-2Db and H-2Kb molecule, respectively. The bm14 Db mutation results in specific failure of female bm14 mice to generate a cytotoxic T lymphocyte (Tc) response to the male-specific antigen H-Y. The allospecific Tc response of CD8+ B6T cells against bm6 Kb mutant spleen cells, in contrast to that against other Kb mutants, is absolutely CD4+ T helper cell dependent. Purified CD8+ T cells completely fail to respond. We now report that the inability to mount these specific immune responses is restored by the use of dendritic cells (DC) as antigen-presenting cells (APC). Comparison of MHC expression on various types of APC by cytofluorimetry and quantitative immunoprecipitation showed very high expression of class I and class II MHC molecules on DC. Strikingly, examination of class I and class II molecules by isoelectric focusing revealed qualitative differences as well. We show that the surface MHC class I molecules of DC are present in greater quantity and carry on average fewer sialic acids than the same molecules isolated from other APC types such as spleen cells, lipopolysaccharide blasts or concanavalin A blasts. That sialic acids on cell surface molecules, including MHC, may play a role in antigen presentation is suggested by our finding that removal of sialic acids, by neuraminidase, can restore specific responses to nonresponder APC as well.
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PMID:Specific immune responses restored by alteration in carbohydrate chains of surface molecules on antigen-presenting cells. 278 48

The capacity of B cells to serve as stimulator cells for a primary mixed leukocyte reaction (MLR) was evaluated. Percoll-fractionated B cells were stimulated with lipopolysaccharide and dextran sulfate (L/D) or a B cell stimulatory factor (BSF-1)-containing culture supernatant, and then were fixed before being used as stimulator cells to more precisely define the state of activation associated with MLR stimulatory capacity. It was found that unstimulated B cells or B cells stimulated for 1 day with L/D or BSF-1 were incapable of initiating a primary MLR, whereas B cells incubated for 3 days in L/D were potent stimulators. The differential activity of 1 day L/D- and BSF-1-activated B cells compared with 3 day L/D-activated B cells was not related to the amount of the relevant MHC class I or class II alloantigens on these cell populations, because all three groups had large increments in MHC class II expression in the following order: BSF-1 greater than 3 day L/D greater than 1 day L/D, and had little difference in MHC class I expression. Also, all three populations were capable of stimulating both MHC class I- and class II-specific T cell hybrids. It was concluded that the capacity of 3 day L/D-activated cells to stimulate a primary MLR was due to the elaboration of necessary co-stimulator molecules. We evaluated whether interleukin 1 (IL 1) was the co-stimulator involved. That this was not the case was indicated by two findings. First, 3 day-activated L/D cells failed to express IL 1 activity as measured by a highly sensitive IL 1 assay that utilizes the T cell line D10.G4.1. Second, recombinant IL 1 added to MLR cultures containing 1 day L/D- or BSF-1 activated B cells failed to function as a co-stimulator. In contrast, the phorbol ester PMA was a potent co-stimulator in this system. We conclude from these experiments that appropriately activated B cells can function as stimulators of a primary MLR, and that they elaborate critical co-stimulator molecules, distinct from IL 1, that enable them to function in this regard.
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PMID:Capacity of B cells to function as stimulators of a primary mixed leukocyte reaction. 294 57

A study was made of the effects of T. b. brucei and the disrupted parasite material on different components of the reactive response of astrocytes in primary cultures prepared from neonatal rats and C6 glioma cells. The effects were compared with lipopolysaccharide (LPS) and fragments of the C6 cells. The disrupted trypanosome material, LPS and C6 fragments caused dose--and time--dependent alterations in morphology of the primary cultures from flat to stellate shape, increases in levels of glial fibrillary acidic protein (GFAp) and enhanced MHC class I and II expression. Exposure to trypanosome material and C6 fragments caused marked increases in phagolysosomes and lysosomes in the primary cultures. The findings demonstrate that T. b. brucei products and astrocyte cell debris are internalized and initiate astrogliosis in vitro.
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PMID:Trypanosoma brucei products activate components of the reactive response in astrocytes in vitro. 749 94

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


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