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)

F1 hybrid New Zealand Black (NZB) x New Zealand White (NZM) (NZB/NZW) mice spontaneously develop an autoimmune disease analogous to systemic lupus erythematosus (SLE). Testosterone experts a powerful suppressive effect on this disorder in adult NZB/NZW mice. A series of experiments was designed to determine if disease would also be suppressed by exposing fetal NZB/NZW mice to increased testosterone. A model was developed in which NZB dams carrying NZB/NZW fetuses were treated with testosterone in a dose adequate to masculinize the external genitalia in female fetuses. NZB/NZW mice that were derived from testosterone-treated dams and control NZB/NZW offspring were followed in a longevity study and had serial assays to assess development of SLE. Additional experiments were carried out to measure lymphocyte subsets and responses to mitogens. Results were compared with F1 hybrid offspring of C57BL/6 dams crossed with DBA/2 males, which are not autoimmune and do not develop SLE. Spleen cells from these groups were tested for Thy 1.2, CD4, CD8, and IgM receptors, and for responses to the mitogens Concanavalin A (ConA) and lipopolysaccharide. Control male NZB/NZW fetuses had unexpectedly high serum estradiol, which decreased significantly with maternal testosterone treatment. The testosterone-exposed male NZB/NZW fetuses developed into adults that lived longer than male NZB/NZW controls. Testosterone treatment of the dam was associated with elevated terminal anti-DNA levels but did not alter markers of renal diseases in adult NZB/NZW mice of either sex. Testosterone-exposed NZB/NZW females had altered T-lymphocyte subsets and testosterone-exposed males had increased response to ConA compared to controls. In male NZB/NZW fetuses whose mothers were administered testosterone, the naturally high level of circulating estradiol observed in untreated male fetuses was decreased significantly. This decrease was associated with an increase in longevity. This unique observation has important implications for fetal exposure to endocrine disruptors in the environment.
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PMID:Effects of altered prenatal hormonal environment on expression of autoimmune disease in NZB/NZW mice. 888 4

Multiple-organ failure is considered a consequence of autodestructive inflammatory response during which a state of immunosuppression is produced. Alterations in CD4 and CD8 lymphocytes after experimental endotoxic challenge and their correlation with the protective effects of interleukin-1beta (IL-1beta) and ibuprofen pretreatment were investigated. CBA/H mice were injected with lipopolysaccharide (LPS) of Escherichia coli (125 mg/kg); 40 mice were pretreated with IL-1beta (80 ng/mouse, 24 hr pre-LPS), 40 with ibuprofen (1 mg/kg 1 hr pre-LPS, 1 mg/kg 30 min post-LPS), and 40 with both drugs (same doses and timing). Prostaglandin E2 (PGE2) urine levels were determined 4, 8, and 12 hr post-LPS (10 mice), CD4 and CD8 cells 24 hr post-LPS (10 mice), and mortality at 24, 48, 72, and 96 hr (20 mice). PGE2 decreased in ibuprofen-treated groups (P < 0.05 versus control, IL-1beta groups). CD4/CD8 ratio increased in groups treated with IL-1beta (11,9) and IL-1beta plus ibuprofen (11,2) compared with sham (3,4), LPS (4,2), and ibuprofen alone (4,1) (P < 0.05). Mortality decreased in all treated groups. A correlation was observed between IL-1beta treatment, CD4/CD8 ratio, and reduced mortality. In this model IL-1beta treatment improved survival after endotoxin challenge, preventing lymphocyte derangements and increasing CD4/CD8 ratio. This effect was not potentiated by ibuprofen administration.
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PMID:Interleukin-1beta and ibuprofen effects on CD4/CD8 cells after endotoxic challenge. 889 11

Using a monoclonal antibody to CD4 we have shown that occupation of CD4 on T cells induces a strong dose dependent inhibition of in vitro IgM plaque forming cell (PFC) response of spleen cells to the T dependent antigen (Ag), sheep red blood cells (SRBC), in Mishell-Dutton cultures. This inhibitory effect is not due simply to nonspecific perturbation or Fc binding, since F(ab) fragments of anti-CD4 are as potent as the intact antibodies, whereas antibodies to class I molecules or T cell CD5 have no effect. The anti-CD4 antibody appears to block contact dependent interaction between T and B cells and this inhibitory effect cannot be overcome by cytokines. Anti-CD4 did not inhibit the PFC response to the T independent antigen, trinitrophenylated lipopolysaccharide. The anti-CD4 antibody prevented the interaction of preactivated fixed SRBC specific T helper cells with B cells, suggesting that CD4 had a role in contact mediated interactions between T cells and B cells. Surprisingly, antibodies to CD40L failed to inhibit the SRBC specific PFC response. Thus CD4 appears to be an important molecule required for cognate interactions between T and B cells that are needed to generate an Ag specific PFC response.
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PMID:A role for T cell CD4 in contact mediated T dependent B cell activation. 891 82

The rat monoclonal antibody LR-1 was initially described to be reactive with an antigen present on murine splenic B lymphocytes. However, flow-cytometric analyses of cells obtained from thymus, bone marrow, spleen, and lymph nodes showed that LR-1 stained approximately 95, 95, 60-70 and 20% of cells present within these tissues in normal DBA/2 mice. The marker recognized by LR-1 was present on peripheral erythrocytes and splenic dendritic cells, and activation with lipopolysaccharide A further increased expression of this antigen by splenic B cells. This particular tissue and cellular distribution was similar to that delineated with monoclonal antibodies reactive with heat-stable antigen (HSA). Duallabelling studies were conducted to compare the reactivity patterns of LR-1 and the HSA-reactive monoclonal antibody J11d and indicated that both antibodies recognized splenocytes bearing B cell (IgM) or erythroid (TER-119, CD71) but not T cell (CD4, CD8) markers. Splenocytes exposed to phosphoinostol-specific phospholipase C showed marked reduction in LR-1 binding, indicating that this antibody recognized a glycosylphosphatidylinositol-anchored cell surface protein, consistent with the known structure of HSA. Mixing of LR-1 with the HSA-specific antibodies J11d or M1/69 provided flow-cytometric profiles indistinguishable from those obtained with either antibody alone. However, LR-1 inhibited M1/69 binding to splenocytes by 83%, while J11d reduced M1/69 binding to these cells by only 18%. This finding suggested that LR-1 and M1/69 recognize identical splenic HSA epitopes, while LR-1 and J11d bind distinct antigenic determinants of spleen HSA. Western blot analysis of splenocyte, thymocyte, bone marrow cell and erythrocyte detergent extracts revealed that LR-1 reacted with glycoforms of HSA of known molecular weights (30-55 kD). Thus, LR-1 recognizes HSA, the murine analogue of human CD24, and will be a useful reagent with which to investigate the role of HSA in the immune response and hematopoiesis.
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PMID:Monoclonal antibody LR-1 recognizes murine heat-stable antigen, a marker of antigen-presenting cells and developing hematopoietic cells. 891 16

We describe a new method to recover and study cells present in the dermis of mouse ear at homeostasis or after intradermal injection of disturbing agents (lipopolysaccharide or Listeria monocytogenes). The ears either left untreated or inoculated were handled and processed as culture explants of the dorsal and ventral leaflets, their dermal sides being spread on a buffered medium. Within this medium emigrate/sediment, with different kinetics: neutrophils, mononuclear phagocytes, dendritic leucocytes, T lymphocytes expressing either gamma delta or alpha beta TCRs, and other minor subsets, the identification of which deserves more relevant reagents: they are likely to be NK, mast cells, eosinophils and their local progenitors. All the major subsets were identified through a combination of immunocytochemical and flow cytometry labeling. Two examples illustrating the advantages and limitations of this new method are given: either 1 microgram of LPS or 10(4) Listeria monocytogenes were injected within the ear 48, 24, 12, 6, 3 h before ear explant culture. This ear explant culture has been further compared to the ear sheet treatment with collagenase/disease for three cell populations, the epidermal dendritic leucocytes, the gamma delta epidermal T cells as well as the alpha beta T cells recirculating within the steady state dermis. This method provides the first evidence of the existence of recirculating T CD4 lymphocytes in the mouse dermis.
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PMID:A method to recover, enumerate and identify lymphomyeloid cells present in an inflammatory dermal site: a study in laboratory mice. 896 94

This study was designed to see whether alterations occur in peripheral blood mononuclear cell phenotype and function in children with Shigella dysenteriae 1 infection with complications (leukemoid reaction and/or hemolytic-uremic syndrome) and whether there are any alterations prior to the development of complications. The following groups of children (ages, 12 to 60 months) were compared: children without any infection (n = 51), children with uncomplicated shigellosis (n = 65), children admitted with complicated shigellosis (leukemoid reaction and/or hemolytic-uremic syndrome) (n = 29), and children with shigellosis who developed complications after enrollment (subsequently complicated shigellosis) (n = 12). Tests for the peripheral blood mononuclear cell phenotype (CD3, CD4, CD8, CD57 [corrected], CD20, and CD25), spontaneous proliferation, and the proliferative response to phytohemagglutinin, pokeweed mitogen, and the lipopolysaccharide of S. dysenteriae 1 were performed, as were skin tests for delayed-type hypersensitivity (DTH). Children who subsequently developed complications differed from other groups of children as follows: (i) the numbers of CD3+ and CD4+ cells were lower than in uninfected children (P < 0.05), (ii) the CD4/CD8 ratio was lower than in children with uncomplicated shigellosis (P < 0.05) and in uninfected children (P < 0.05), and (iii) the levels of spontaneous proliferation of peripheral blood mononuclear cells were higher and DTH responses were lower than those in children with uncomplicated shigellosis (P < 0.05 and P < 0.017, respectively). Children with complications differed by having (i) increased numbers of CD3- CD57- [corrected] CD20- cells (P < 0.05) compared with those in other groups of children and (ii) lower CD4/CD8 ratios (P < 0.05), higher levels of spontaneous proliferation (P < 0.05), and lower DTH responses (P = 0.005) than children with uncomplicated shigellosis. Three to five days after enrollment, the number of CD4+ cells increased in children who subsequently developed complications (P = 0.025), i.e., when they developed complications and at this time their CD4+ cell number was similar to that of other groups of children. Thus, lymphocyte phenotype and function are altered prior to the development of complications in children with shigellosis, and once complications develop, the pattern of alterations changes. Whether these alterations have a role in precipitating complications or whether they reflect early events underlying the development of complications remains to be elucidated.
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PMID:Alterations in lymphocyte phenotype and function in children with shigellosis who develop complications. 899 34

Autoimmune-prone MRL/lpr mice, homozygous for the lpr mutation, exhibit defective apoptosis and develop generalized lymphoproliferation with the accumulation of a double-negative (DN: CD4- CD8-) T cell population. The capacity of lpr T lymphocytes to effectuate Fas- and perforin-mediated cytotoxicity was investigated. Spleen and lymph nodes cells spontaneously lyse Fas- targets (thymocytes) through a Fas-mediated mechanism as a consequence of their overexpression of Fas ligand (FasL) confirmed by semiquantitative reverse transcription (RT)-PCR and immunoprecipitation analysis. This cytotoxicity was greatly increased after stimulation of the effectors by phorbol myristate acetate (PMA) + ionomycin. Under these conditions, MRL/lpr spleen and LN cells exhibited strong Fas-mediated Ca2+-independent cytotoxic activity against wild-type Fas+ (H-2 compatible or incompatible) thymocytes or lipopolysaccharide (LPS)-transformed blast cells. Such Fas-mediated cytotoxic activity was also observed with C57BL/6-lpr, but never with wild-type C57BL/6 or MLR+/+ effectors. Depletion experiments showed that the effector cells of this Fas-mediated cytotoxicity were DN T cells. This subset, which represent in vivo activated T cells, can spontaneously lyse Fas+ targets by a mechanism that does not need the interaction of the T cell receptor (TCR) with major histocompatibility complex molecule plus antigen. This lytic potential is increased by PMA + ionomycin, which sends a second activation signal to these primed T cells. Therefore, the small amounts of Fas receptor expressed on MRL/lpr tissues may account for their nonspecific autoimmune attack by DN cells. In Con A-containing medium, which allows detection of the perforin-mediated pathway against Fas targets, cytotoxic CD8+ effectors were detected that are able to kill lpr thymocytes via a Ca2+-dependent pathway. Thus, in MRL/lpr mice, these CD8+ cells could constitute potent cytotoxic effectors against cells presenting antigen to their TCR.
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PMID:MRL/lpr CD4- CD8- and CD8+ T cells, respectively, mediate Fas-dependent and perforin cytotoxic pathways. 904 12

Bacterial cell wall products such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP) have the capacity to enhance immune responses to antigens. The expression of surface class II major histocompatibility antigens and the costimulatory receptors CD18 and CD54/ICAM-1 (intercellular adhesion molecule) was used to evaluate the comparative influence of these immunostimulators. On monocytes, both LPS and MDP increased the expression of human leukocyte antigen (HLA)-DR (maximal at 6 hr), CD18 (maximal at 1-3 hr), and ICAM-1 (maximal at 18-24 hr for LPS and 12 hr for MDP) without increasing the production of superoxide. MDP-induced ICAM-1 expression on monocytes returned to baseline values after 12 hr. On lymphocytes, only LPS increased ICAM-1 (after 18 hr) without affecting CD18, and a differential analysis demonstrated a generalized ICAM-1 upregulation in lymphocyte subsets after 18 hr: the most pronounced effect was measured in natural killer cells, followed by CD8(+) T cells, B cells, and CD4(+) T cells. MDP did not alter ICAM-1 or CD18 expression on lymphocytes. These similar but smaller effects of MDP may, in part, explain the lesser toxicity of MDP when compared to LPS.
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PMID:Bacterial cell wall products increase monocyte HLA-DR and ICAM-1 without affecting lymphocyte CD18 expression. 907 85

T lymphocytes may play a central role in MS. The search for more targeted immunosuppression than is currently available has led to recent clinical trials of novel therapeutics. We studied 29 patients in a double-blind placebo-controlled trial of the chimeric monoclonal anti-CD4 antibody, cM-T412 (Centocor, Leiden, Holland) over a period of 18 months. Total and differential WBC counts; T, B, and natural killer lymphocytes; CD4+ and CD8+ T cells; CD4+ and CD4- naive cells; CD4+ and CD4- memory cells; interleukin-2 receptor- and major histocompatibility class II-positive T cells; serum tumor necrosis factor alpha (TNF-alpha); and PHA (phytohemagglutinin)/LPS (lipopolysaccharide)-stimulated whole blood TNF-alpha production were all examined serially in peripheral blood for the duration of the trial. In addition, for the first two treatment cycles, the above variables were tested 1 and 7 days after treatment. The results demonstrated significant long-term reductions, lasting up to 12 months after the last treatment cycle in all CD4+ subsets studied, but with a relative preservation of CD4+ memory cells as opposed to CD4+ naive cells. CD4- subsets also showed significant reductions after treatment but returned to baseline levels within 7 days. Monocyte counts were unaffected by cM-T412. Serum TNF-alpha and 2- and 18-hour PHA/LPS-stimulated TNF-alpha levels were also unchanged in the long term, although significant increases were observed in the 2- and 18-hour PHA/LPS-stimulated TNF-alpha levels the day immediately after treatment. There was no significant correlation between any of the immunologic markers studied and MRI measures of disease activity.
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PMID:Effects of anti-CD4 antibody treatment on lymphocyte subsets and stimulated tumor necrosis factor alpha production: a study of 29 multiple sclerosis patients entered into a clinical trial of cM-T412. 910 60

Salmonella abortusovis infection leads to ovine abortion. The basis for immunity against this infection is unknown. Immune responses were studied from prescapular lymph node (PSLN) cells of sheep infected with either a subcutaneous inoculation of virulent (15/5) or a vaccine (Rv6) strain and compared with those of uninfected sheep. PSLN cell phenotypes were characterized by immunofluorescence staining associated with flow cytometry. The in vitro responses were analysed using the PSLN cell proliferative response to several antigens, their secreted IL-2-like activities and their level of nitric oxide (NO) release. The phenotype analyses showed that the CD4(+)-T cell percentages decreased whereas B and MHC-II+ cell percentages increased in the infected sheep. This phenomenon occurred earlier for the virulent strain. The PSLN enlargement was greater and in vitro proliferation more frequent for the sheep infected with the virulent strain compared with the vaccine-infected ones. Proliferation occurred as a result of cell exposure to whole killed bacteria or to the cell wall fraction from S abortusovis but not to the homologous lipopolysaccharide. The secreted IL-2-like activities increased in parallel. The mitogenic response to concanavalin A decreased for infected sheep. For infected sheep, the level of NO release was maximal at the beginning of the infection. It was downregulated by in vitro exposure to S abortusovis antigens but remained unchanged for concanavalin A. NO release was not detected in uninfected sheep. This preliminary investigation provided some keys to the understanding of ovine response to S abortusovis infection and suggested that it shared common features with the mouse immune response.
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PMID:In vitro cellular responses from sheep draining lymph node cells after subcutaneous inoculation with Salmonella abortusovis. 911 38


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