Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with malignant brain tumors have a variety of immunologic abnormalities, including the impaired responsiveness of peripheral blood lymphocytes (PBL) to mitogens and alloantigens. We further investigated this impairment of lymphocyte reactivity by employing the techniques of limiting dilution analysis and cytokinetic analysis. PBL preparations from patients have approximately six times fewer phytohemagglutinin (PHA)-responsive cells than PBL from normal subjects. Similar results were obtained with purified T cell preparations. Cytokinetic analysis of PHA-induced [3H]thymidine incorporation employing colchicine blocking of mitosis demonstrated that the number of first generation cells entering the S-phase of mitosis for each 24-hr period was less for PBL from patients than for PBL from normal individuals. First generation responding cells from patients and normal subjects entered DNA synthesis at the same time (48 to 72 hr). Cytokinetic analysis over a period of 168 hr demonstrated that whereas PBL from normal individuals demonstrated second generation responding cells, PBL from the majority of patients did not, thus indicating a defect in their ability to undergo clonal expansion. Measurement of interleukin 2 (IL 2) activity in culture fluids from PHA-activated PBL from normal subjects and patients revealed significantly lower IL 2 levels in culture fluids from PBL from patients. The addition of various concentrations of lectin-free IL 2 to PBL from patients stimulated with PHA did not restore responsiveness to normal values. There was no difference between the levels of interleukin 1 (IL 1) produced by lipopolysaccharide-activated monocytes from normal subjects and patients. Overall, these results suggest that an intrinsic defect exists in T cells obtained from brain tumor patients that renders them unable to enter into normal mitogen-induced blastogenesis.
 ...
PMID:Cytokinetic basis for the impaired activation of lymphocytes from patients with primary intracranial tumors. 631 91

We have used a monoclonal antibody (Mab) to the interleukin 2 (IL 2) receptor as well as a Mab to the transferrin receptor to analyze the effects of cyclosporin A (CsA) on the induction and expression of these activation antigens on mitogen-stimulated murine T and B lymphocytes. The same concentration (0.25 microgram/ml) of CsA that produced optimal inhibition of the T cell proliferative response to concanavalin A (Con A) was also very effective at inhibiting IL 2 production and the induction of IL 2 responsiveness, as well as the expression of the IL 2 and transferrin receptors when measured 72 hr after mitogen activation. Surprisingly, CsA only minimally inhibited expression of these receptors 24 hr after the addition of mitogen; however, T cell blasts recovered from these cultures failed to respond to IL 2 even though IL 2 receptor expression was only modestly decreased. These results suggest that inhibition of the maturation of receptor expression is secondary to an early effect of CsA in blocking the induction of IL 2 responsiveness or to an arrest in the sequence of events required for maturation of T cells that bear high densities of these receptors. In contrast to the results observed with T lymphocytes, CsA had no effect on the B cell proliferative response to lipopolysaccharide (LPS) or on the induction of the IL 2 and transferrin receptors on activated B lymphocytes.
 ...
PMID:Differential effect of cyclosporin A on the expression of T and B lymphocyte activation antigens. 632 23

The SPI-802 human leukemia cell line, which possesses E receptors and used to have natural killer activity, has been demonstrated to produce high levels of interleukin 1 (IL-1)-like activity. SPI-802 supernatants prepared in 1% serum-containing cultures with lipopolysaccharide stimulation, like similarly prepared adherent-cell-derived IL-1, enhanced phytohemagglutinin-induced mouse thymocyte proliferation. When adherent-cell IL-1 gave 50% maximum activity at a reciprocal dilution of 20, SPI-802 supernatant gave it at 200, indicating the production of high levels of IL-1-like activity by the cell line. SPI-802 supernatant promoted the production of interleukin 2 (IL-2) by the Jurkat-F1884 T-cell line: Levels of IL-2 activity obtained with 15% SPI-802 supernatant were almost equivalent to those obtained with 50% adherent-cell IL-1 as estimated by the maximum proliferation of IL-2-dependent cytotoxic T cells. SPI-802 supernatant by itself exhibited no IL-2 activity. Major IL-1-like activity of SPI-802 supernatant was present in fractions from AcA54 columns corresponding to Mr 12,000-20,000 and 60,000-70,000 and resolved on isoelectrofocusing into two distinct species with pI values of 5.0 and 7.0, being consistent with the results of adherent-cell IL-1. The SPI-802 cell line having E receptors is an ideal source of a soluble factor with the biological and biochemical characteristics of human IL-1.
 ...
PMID:Production of high levels of interleukin 1-like activity by the SPI-802 human leukemia cell line with E receptors. 633 84

We have observed that CT6 cell line, a murine interleukin 2 (IL 2)-dependent T cell line, was highly responsive to phorbol myristate acetate (PMA) and to a lesser extent but significantly responsive to lipopolysaccharide (LPS) in the short-term proliferation assay. In contrast, two other murine IL 2-dependent cell lines, CTLL-2 and NK clone 7, were totally unresponsive to these stimulants. Even when CT6 was recloned by a limiting dilution, no unresponsive clone to PMA was obtained, whereas several clones unresponsive to LPS were obtained. PMA, unlike to IL 2, could not support a long-term culture of CT6. There are no differences between CT6 and CTLL-2 except that the former possessed asialo GM1 while the latter lacked it. Though it is unknown whether this difference is involved in the mechanism of the response of CT6 to PMA or LPS, these data give caution to us against the use of CT6 for the determination of IL 2 activity contaminated with PMA and LPS.
 ...
PMID:Interleukin 2-dependent T cell line acquires responsiveness to phorbol myristate acetate and lipopolysaccharide in the course of long-term culture. 633 28

Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals.
 ...
PMID:Lymphoid abnormalities in rats with adjuvant-induced arthritis. I. Mitogen responsiveness and lymphokine synthesis. 633 88

Mice injected with Propionibacterium acnes, when challenged with lipopolysaccharide release a range of soluble mediators into their serum. Included among these is lymphocyte activating factor (LAF, interleukin-1). The release of LAF in vivo was detected only when serum samples were assayed at high dilution because inhibitors of its activity in vitro were also present. The kinetics of release of LAF in vivo after injection of P. acnes was dependent on the mouse strain used. LAF was also detected in serum collected from nude mice, implying that the LAF activity measured in vitro was not due to contamination with T cell products, such as interleukin 2.
 ...
PMID:Production of lymphocyte activating factor in vivo. 636 Aug 52

Groups of C57BL/6 mice were infected either intravenously or subcutaneously with 10(5) or 10(8) Mycobacterium lepraemurium cells, and the ability of their splenic macrophages and T-cells to produce, respectively, interleukin 1 on lipopolysaccharide stimulation and interleukin 2 on concanavalin A stimulation was assessed during the course of infection. In all groups of infected mice, interleukin 1 production remained unaffected during the entire observation period, whereas interleukin 2 activity decreased as the infection progressed. Heavily infected mice (10(8) M. lepraemurium cells) showed an earlier and stronger deficiency interleukin 2 production by concanavalin A-stimulated spleen cells than did mice infected with a lower dose (10(5) bacilli), without detectable influence by the route of inoculation. In mice receiving 10(5) bacilli, minor differences were seen according to the route of infection, with a slight delay in interleukin 2 decrease in mice injected intravenously. In subcutaneously inoculated mice, the failure of spleen cells to produce interleukin 2 after concanavalin A stimulation did not correlate with the number of bacilli developing in the spleen, suggesting the existence of suppressor mechanisms acting at a distance from the site of inoculation.
 ...
PMID:Influence of dose and route of Mycobacterium lepraemurium inoculation on the production of interleukin 1 and interleukin 2 in C57BL/6 mice. 637 13

In order to obtain an anti-interleukin 2 (IL 2) receptor antibody, we immunized mice with phorbol myristate acetate-pulsed rat T lymphoblasts. The spleen cells of the mice were fused with myeloma cells. Several stable clones of hybridoma cells were obtained that produced monoclonal antibodies (mAb) reacting specifically with rat T lymphoblasts. Only one of these mAb, the mAb ART18, showed characteristics of a putative anti-IL 2 receptor antibody. This mAb was produced on a large scale, purified, and characterized. As tested by a binding assay, 125I-labeled mAb ART18 bound to rat T lymphoblasts (7.5 X 10(4) binding sites per cell), but not to thymocytes or spleen cells of rat origin, or to lymphoblasts, thymocytes, or spleen cells of murine origin. Only marginal binding to lipopolysaccharide-stimulated rat lymphoblasts was detected. The mAb ART18 inhibited in a species-specific and dose-dependent manner i) the capacity of rat T lymphoblasts to absorb IL 2 activity and ii) the capacity of rat T lymphoblasts to proliferate in response in IL 2. The function of T lymphoblasts of murine origin was not affected by the mAb ART18. The time course of the acquisition by mitogen-stimulated spleen cells of the capacity to absorb IL 2 activity was paralleled by that of their capacity to bind 125I-labeled mAb ART18. According to these data, the mAb ART18 seems to be directed against an antigenic determinant of the IL 2 receptor molecule.
 ...
PMID:The characteristics of a monoclonal antibody that binds specifically to rat T lymphoblasts and inhibits IL 2 receptor functions. 640 Nov 87

Xenogeneic monoclonal antibodies were prepared to the murine interleukin 2 (IL-2)-dependent HT2 cell line. One rat IgM monoclonal antibody (7D4) was identified that inhibited proliferation of the HT2 cells and of IL-2-dependent CTLL cells in the presence of crude rat IL-2 as well as of purified human IL-2. The level of inhibition was dependent on both antibody and IL-2 concentration. Cell distribution studies using a fluorescence-activated cell sorter showed that the antigen identified by 7D4 is expressed at a high density on HT2 cells and on concanavalin A (Con A)-induced T-cell blasts and at a substantially lower density on lipopolysaccharide-induced B-cell blasts; 7D4 binding was not detected on greater than 95% of nonactivated thymocytes, T cells, or B cells. Competition binding studies indicated that 7D4 fails to inhibit the binding of 3H-labeled human IL-2 to CTLL cells. However, 7D4 specifically immunoprecipitated 3H-labeled human IL-2 from detergent extracts of HT2 cells or Con A-induced T-cell blasts that had been pulsed with [3H]IL-2; in contrast, 7D4 did not react with free [3H]IL-2. Initial biochemical analysis of immunoprecipitates with 7D4 of detergent extracts from surface-iodinated Con A-activated spleen cells showed a major band having apparent molecular weight of 48,000-62,000. Collectively, these results suggest that 7D4 detects an epitope on the IL-2 receptor distal to the ligand binding site or another molecule that physically associates with the receptor.
 ...
PMID:Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex. 641 30

Murine peritoneal exudate cells (PEC) treated with murine recombinant interferon-gamma (IFN-gamma) (greater than 99% estimated purity), or concanavalin A-stimulated spleen cell supernatants developed tumoricidal properties (macrophage activation factor [MAF] activity). MAF activity was found to occur with treatments of 10 U/ml IFN-gamma, and at levels as low as 1 U/ml IFN-gamma if a second signal (5 ng/ml endotoxin) was present in the MAF assay. Endotoxin (lipopolysaccharide [LPS]) alone at these levels failed to induce MAF; induction of MAF was observed at 1,000-fold greater levels. The ability of IFN-gamma to stimulate murine PEC was species specific. Various sources of materials that displayed MAF activity, including supernatants from interleukin 2-dependent cloned cytotoxic murine T lymphocyte lines that did not display detectable antiviral activity, were neutralized by antibody raised and affinity purified against recombinant IFN-gamma. Thus, IFN-gamma, although never detectable by antiviral assays, appears to be present in many lymphokine preparations and has potent macrophage activation capability.
 ...
PMID:Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor. 642 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>