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)

Recently, it was reported that nitric oxide (NO) directly controls intracellular iron metabolism by activating iron regulatory protein (IRP), a cytoplasmic protein that regulates ferritin translation. To determine whether intracellular iron levels themselves affect NO synthase (NOS), we studied the effect of iron on cytokine-inducible NOS activity and mRNA expression in the murine macrophage cell line J774A.1. We show here that NOS activity is decreased by about 50% in homogenates obtained from cells treated with interferon gamma plus lipopolysaccharide (IFN-gamma/LPS) in the presence of 50 microM ferric iron [Fe(3+)] as compared with extracts from cells treated with IFN-gamma/LPS alone. Conversely, addition of the iron chelator desferrioxamine (100 microM) at the time of stimulation with IFN-gamma/LPS increases NOS activity up to 2.5-fold in J774 cells. These effects of changing the cellular iron state cannot be attributed to a general alteration of the IFN-gamma/LPS signal, since IFN-gamma/LPS-mediated major histocompatibility complex class II antigen expression is unaffected. Furthermore, neither was the intracellular availability of the NOS cofactor tetrahydrobiopterin altered by treatment with Fe(3+) or desferrioxamine, nor do these compounds interfere with the activity of the hemoprotein NOS in vitro. We demonstrate that the mRNA levels for NOS are profoundly increased by treatment with desferrioxamine and reduced by Fe(3+). The half-life of NOS mRNA appeared not to be significantly altered by administration of ferric ion, and NOS mRNA stability was only slightly prolonged by desferrioxamine treatment. Nuclear run-off experiments demonstrate that nuclear transcription of cytokine-inducible NOS mRNA is strongly increased by desferrioxamine whereas it is decreased by Fe(3+). Thus, this transcriptional response appears to account quantitatively for the changes in enzyme activity. Our results suggest the existence of a regulatory loop between iron metabolism and the NO/NOS pathway.
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PMID:Iron regulates nitric oxide synthase activity by controlling nuclear transcription. 752 Apr 77

We investigated parameters that affect the efficiency with which antigenic epitopes from Salmonella typhimurium are processed for presentation to T lymphocytes. As a model system, the hen egg white lysozyme 52-61 [HEL(52-61)] epitope, which binds the murine major histocompatibility complex class II (MHC-II) molecule I-Ak, was expressed in soluble fusion proteins in S. typhimurium. Murine peritoneal macrophages mediated phagocytic processing of viable S. typhimurium expressing fusion proteins of the HEL epitope for presentation via I-Ak regardless of the bacterial compartment in which the epitope was contained (i.e., surface exposed, facing the periplasmic space, or in the cytoplasm). Minor differences in processing efficiency observed with different epitope compartmentalizations could be overcome by altering the relative expression level, indicating that epitope abundance is an important factor for efficient processing of epitopes from S. typhimurium. This processing pathway required phagocytosis of bacteria followed by passage through an acidic compartment, suggesting a pathway involving phagolysosomal degradation of the bacteria to liberate epitopes that bind MHC-II. HEL(52-61) was processed more efficiently from heat-killed S. typhimurium than from viable bacteria, and in addition, the HEL epitope was processed more efficiently from a rough lipopolysaccharide (LPS) strain than from its isogenic smooth LPS counterpart, most likely because of enhanced phagocytosis of the rough LPS strain. These data suggest that the efficiency of epitope processing from S. typhimurium for presentation via MHC-II is affected by bacterial viability, epitope abundance, and LPS phenotype, factors which may be important to consider in development of recombinant S. typhimurium vaccine strains.
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PMID:Parameters that influence the efficiency of processing antigenic epitopes expressed in Salmonella typhimurium. 752 93

Intraportal inoculation of CC531 adenocarcinoma cells into syngeneic rats causes an increase of liver macrophage cell number but not of major histocompatibility complex class II antigen expression. On day 1 after inoculation of 10(5) CC531 cells, a fixed number of isolated liver macrophages lysed significantly more target cells in vitro than did control cells. This effect was still present after 4 weeks. A 10-fold higher initial tumor dose significantly suppressed the macrophage response during the first 2 weeks. In contrast to tumoricidal activity induced by lipopolysaccharide in vitro, the tumoricidal response following in vivo challenge with tumor cells appeared not closely related to the production of reactive nitrogen intermediates, as in the latter case it was not abrogated in the presence of nitric oxide synthase inhibitor. Furthermore, the liver macrophage population appeared not fully activated after tumor inoculation as lipopolysaccharide further increased tumoricidal activity in vitro. The observed numerical and functional response of liver macrophages to intraportally inoculated tumor cells points at an important role of these cells in aspecific immune reactivity aimed at the reduction of local tumor growth. Results suggest that mechanistic differences exist between macrophage tumoricidal activity induced by tumor cells as compared with lipopolysaccharide.
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PMID:Tumoricidal response of liver macrophages isolated from rats bearing liver metastases of colon adenocarcinoma. 753 89

We have previously found that thymic B cells, particularly thymic CD5+ B cells, show low responsiveness to the usual B cell stimulants such as lipopolysaccharide or anti-IgM plus interleukin (IL)-4, although they proliferate and produce antibodies after direct interaction with major histocompatibility complex class II-restricted T blasts. These findings raise the possibility that a CD40-CD40 ligand (L) interaction is involved in the activation of thymic B cells. In the present study, we therefore examine this possibility using CD40L-transfected Chinese hamster ovary (CHO) cells or anti-CD40 monoclonal antibody (mAb). When B cells in the spleen and peritoneal cavity were stimulated, they proliferated and produced immunoglobulin (Ig) in the presence of CD40L-CHO cells or anti-CD40 mAb alone. However, another signal delivered by IL-10 in addition to CD40L-CHO cells or anti-CD40 mAb was found to be necessary for thymic B cells to proliferate and secrete Ig. Other interleukins acting on B cells, such as IL-4, IL-5, and IL-6, had no effect on the activation of thymic B cells, which thus have unique characteristics not found in peripheral B cells. This report discusses the physiological significance of IL-10- and CD40-driven signals in the activation of thymic B cells.
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PMID:Activation of thymic B cells by signals of CD40 molecules plus interleukin-10. 753 53

Four monoclonal antibodies (mAbs), UC-A4, UC-D3, UC-H9, and IL-A21, specific for bovine major histocompatibility complex class II proteins are described. Sequential immunoprecipitation experiments using biotin-labeled peripheral blood mononuclear cells suggested, but did not conclusively establish, that each of these antibodies recognized a different epitope. The epitope identified by IL-A21 appeared to be common to all of the class II proteins precipitated by the four mAbs, and UC-D3 and UC-H9 each appeared to react with distinct epitopes on separate subsets of these class II proteins. Monoclonal antibody UC-A4 appeared to identify an epitope on a subset of the class II molecules identified by UC-H9. Differences found in the expression by lymphoid cells of class II proteins identified by the four mAbs were indicative of each mAb recognizing a different epitope. UC-H9 and IL-A21 class II proteins were detected on all surface immunoglobulin (S'Ig) positive cells in peripheral blood, but UC-A4 and UC-D3 class II proteins were not. Expression of UC-A4 class II proteins, detected at low density on a strikingly reduced number of S'Ig+ cells from the blood of some bovine leukosis virus-infected cattle, could be increased by culturing these B cells with lipopolysaccharide. All peripheral blood monocytes expressed UC-H9 and IL-A21 class II proteins, but only a proportion of monocytes expressed detectable UC-A4 and UC-D3 class II proteins. Almost all mitogen-stimulated BoCD4+ and BoCD8+ T cells expressed UC-H9 and IL-A21 class II proteins, whereas fewer stimulated T cells of both subsets expressed UC-A4 and UC-D3 class II proteins. All gamma/delta receptor (gamma/delta R) T cells expressed UC-D3, UC-H9, and IL-A21 class II proteins, but no cells (of gamma/delta R+ or CD4+/CD2+ phenotype) from gamma/delta R+ T cell-enriched cultures expressed UC-A4 class II proteins.
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PMID:Differential expression of bovine MHC class II antigens identified by monoclonal antibodies. 768 62

We investigated the in vitro adhesion of 51Cr-labeled lymphocytes to cultured brain endothelial cells and the in vivo expression of intercellular adhesion molecule-1 (ICAM-1) on cerebral endothelial cells in a rat model of experimental allergic encephalomyelitis (EAE) before and after treatment with lipopolysaccharide (LPS). Adhesion of lymphocytes to cerebral endothelial cells was significantly increased in EAE compared with controls (p < 0.01), and was significantly correlated with the percentage of major histocompatibility complex class II antigen-positive cells in lymph node cells (p < 0.001). LPS enhanced ICAM-1 expression on endothelial cells and lymphocyte adhesion to those cells, and caused a significant increase in the in vivo expression of ICAM-1 compared with controls (p < 0.001). Lymphocyte adhesion to endothelial cells was significantly blocked by monoclonal antibodies against ICAM-1, lymphocyte function-associated antigen-1, or very late activation antigen-4. Our findings suggest that lymphocyte adhesion to brain endothelial cells may contribute to lymphocyte migration across the blood-brain barrier in EAE and that LPS may cause progression of EAE lesions.
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PMID:Adhesion of lymphocytes to endothelial cells in experimental allergic encephalomyelitis before and after treatment with endotoxin lipopolysaccharide. 771 50

Dendritic cells (DC) in nonlymphoid organs can internalize and process foreign antigens before migrating to secondary lymphoid tissues to initiate primary immune responses. However, there is little information on which stimuli promote migration of DC from the tissues. Systemic administration of lipopolysaccharide (LPS), which induces in vivo production of cytokines, led to a reduction in the numbers of major histocompatibility complex class II-positive (Ia+) leukocytes in mouse hearts and kidneys: > 95% of DC were depleted 1-3 d after injection of 50 micrograms LPS. Several lines of evidence indicated that this response was due to migration of DC rather than loss of Ia expression or cytotoxic effects. In skin of treated mice, the number of Ia+ epidermal Langerhans' cells (LC) was reduced, and "cords" of Ia+ leukocytes became evident in the dermis. The latter cells expressed little NLDC145 and may have originated from recruited or resident DC progenitors. Systemic administration of recombinant tumor necrosis factor (rhTNF)-alpha resulted in a decrease in numbers of Ia+ cells in heart and kidney and of epidermal LC, and it also induced dermal cords. Administration of a rh-interleukin (IL)-1 resulted in a decrease in Ia+ cells only in renal medulla, appeared to activate a subset of epidermal LC, and induced dermal cords. Similar microgram doses of rhIL-2 had no obvious effect. Treatment with a neutralizing anti-TNF antiserum before LPS administration inhibited the depletion of LC from skin but not from heart or kidney. Therefore, TNF-alpha and IL-1 alpha may promote DC migration from nonlymphoid tissues and may have differential effects on different DC populations, but it is unclear whether they act on DC directly or indirectly (e.g., via other cytokines).
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PMID:Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. 776 9

Cellular adherence is important for monocyte migration and function and is known to induce monocyte activation, leading to the production of mRNA for several proto-oncogenes and cytokines. In addition, since cellular adherence has important intracellular signalling function, it has the potential to enhance human immunodeficiency virus (HIV) replication in monocytic cells. We have investigated the effects of adhesion of the monocytic cell line THP-1 transfected with HIV1 or HIV2 long terminal repeat chloramphenicol acetyltransferase (LTR CAT) constructs. These studies have shown that adherence to tissue culture plastic or confluent endothelial cells is essential for enhanced HIV LTR CAT expression in lipopolysaccharide-stimulated cells. In addition, we have investigated the effects of engagement of specific adhesion molecules, using immobilized antibodies, on HIV replication in the promonocytic cell line OM101, which contains a single latent proviral copy of HIV. Such studies have demonstrated that engagement of CD18, the beta subunit of the lymphocyte function-related antigen-1 (LFA-1) and major histocompatibility complex class II (MHC II) enhanced HIV replication. LFA-1 is involved in both monocyte-endothelial cell interactions and monocyte-T-cell interactions, and MHC II is involved in monocyte interaction with antigen-specific T cells. These data suggest that such interactions of membrane adhesion molecules with their appropriate ligand enhance HIV replication in vivo. Thus, this study has demonstrated that cellular adherence is a key regulatory factor of HIV replication in monocytic cells.
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PMID:Cellular adherence enhances HIV replication in monocytic cells. 780 Sep 38

Interleukin-4 (IL-4) has various activities on B cells and on hematopoietic cells. We previously reported that TUGm2, a monoclonal antibody to the gamma subunit of the IL-2 receptor (IL-2R gamma), inhibited IL-4-dependent proliferation of CTLL2, a cytotoxic T cell line. We proposed that IL-2R gamma is required for the functional IL-4 receptor (IL-4R) in T cells. In the present work, we further examined whether or not IL-2R gamma is involved in IL-4R function in mouse myeloid cell lines and splenic B cells. TUGm2 suppressed the IL-4-induced proliferation of BA/F3 or IC2 cells, as well as of purified splenic B cells. TUGm2 partially suppressed proliferation of B cells induced by the combination of IL-4 and anti-immunoglobulin M (IgM) antibody. In contrast, TUGm2 had no effect on proliferation of B cells induced by anti-IgM antibody alone or lipopolysaccharide (LPS). TUGm2 also inhibited IgE production induced by IL-4 of LPS-stimulated B cells. The induction of major histocompatibility complex class II molecules or CD23 by IL-4 was virtually unaffected by TUGm2 antibody. These results indicate that IL-2R gamma is differentially involved in various IL-4-dependent reactions.
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PMID:Involvement of the interleukin-2 receptor gamma subunit in interleukin-4-dependent activation of mouse hematopoietic cells and splenic B cells. 784 21

An inflammatory reaction, essential for defence against infection and for wound repair, may also induce irreversible tissue damage. It appears that the central nervous system has developed its own immunosuppressive strategy in order to limit the destructive effects of inflammation. To clarify this point, we have characterized in one unique model of inflammation induced in the rat by intracerebral lipopolysaccharide injection the kinetics of the inflammatory reaction, the participation of immunitary and glial cells and of three growth factors. Among these molecules, brain-derived neurotrophic factor mRNA expression was found decreased following LPS injection. No striking differences were observed in the brain parenchyma after stab lesion or inflammatory lesion apart from an increase in the number of monocytes/macrophages recruited early to the lesion area. Macrophages were later accumulated around the lesion when astroglia and microglia reactions occurred. Some of the macrophages and microglia expressed major histocompatibility complex class II antigens on their surface whereas no T or B lymphocytes were observed in the brain parenchyma. However, a subpopulation of CD3- and CD4-negative CD8-positive cells, likely natural killer cells, was observed around the lesion site; this recruitment was inhibited by the highest dose of LPS. This study therefore supports the hypothesis of a suppression of some aspects of cell-mediated immunity in the brain, mechanisms which need to be further characterized.
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PMID:Lipopolysaccharide intracerebral administration induces minimal inflammatory reaction in rat brain. 798 42


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