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)

Mo3e is a protease-sensitive membrane antigen (p75,50) selectively expressed by human monocytic cells (monocytes and U-937 cells) stimulated in vitro by exposure to a variety of activating factors, including phorbol diester compounds, bacterial lipopolysaccharide (LPS), and muramyl dipeptide (MDP)(R.F. Todd et al., J. Immunol. 135, 3869, 1985). Here we report that primary and multiply-passaged cultures of HUVEC also express the Mo3e determinant after stimulation by phorbol myristate acetate (PMA) and related inducers of protein kinase C. As measured in a radioimmunoassay of anti-Mo3e antibody binding to monolayer cultures of HUVEC, unstimulated cells bore little if any Mo3e. After culture for 4-120 hr in medium containing PMA, 4 beta-phorbol dibutyrate, 4 beta-phorbol didecanoate, or mezerein (each at a concentration of 81 nM), or 1-oleoyl-2-acetoyl-sn-3-glycerol (1 mM), HUVEC were found to selectively express the Mo3e determinant. The magnitude of expression was dependent upon the concentration of the stimulus, maximal by 24 hr, and inhibited by cycloheximide. The combination of PMA and the calcium ionophore, ionomycin, had an additive or synergistic effect on HUVEC Mo3e expression. The biologically inactive phorbol compounds 4 beta-phorbol and 4 alpha-phorbol didecanoate failed to stimulate Mo3e expression. Also inactive as inducers of HUVEC Mo3e expression were crude lymphokine and monokine supernatants, recombinant human lymphokines (interferon-gamma and interleukin-2), recombinant human monokines (interleukin-1 and tumor necrosis factor), bacterial cell wall products including LPS and MDP, pharmacologic agents that increase intracellular cyclic adenosine monophosphate (prostaglandin E2, cholera toxin, theophylline, isoproterenol and isobutylmethylxanthine), lectins (Con A and PHA), and heparin. These results indicate that Mo3e is an inducible plasma membrane antigen of not only mononuclear phagocytes but also cultured HUVEC.
 ...
PMID:Expression of Mo3e antigen by cultured human umbilical vein endothelial cells (HUVEC) stimulated by phorbol myristate acetate (PMA) and related pharmacological inducers of protein kinase C. 334 69

The effect of chronic treatment with an immunostimulating agent, bestatin, on age-associated immune decline was assessed in C57BL/6 mice. Animals were given weekly doses of bestatin (100 micrograms/mouse, i.p.) from 7 months of age until death, and immune responses (natural killer cell activity, T cell cytotoxicity in vitro and in vivo, delayed-type hypersensitivity reaction, lymphoproliferative responses to mitogens, production of interleukin-2, macrophage functions) were tested at 11, 15, and 20 months. Most of the functions were reduced in 15-17-month-old mice, but evidence of reduced macrophage activities appeared only in limiting conditions (low lipopolysaccharide stimulation for interleukin-1 production and low concentration of macrophages in the cytostatic test). Bestatin administration produced a transient increase in natural killer (NK) cell activity and in vivo T cell cytotoxicity, followed (15-20 months of age) by a depression of NK and T cell-mediated responses. Only macrophage functions were stimulated in 20-month-old bestatin-treated mice. This unresponsiveness coincides with an accelerated mortality of bestatin-treated mice and a significant increase in the number of spontaneous tumor-bearing animals. The stimulation of T cells by bestatin seems to be mediated by a primary activation of macrophages to release immune mediators. Several reasons for the bestatin-induced immunodepression can be postulated including a high dose of bestatin, leading to toxicity or unresponsiveness; induction of suppressor cells; and overproliferation of T cells due to the mitogenic activity of bestatin, which may act as a promoting factor for tumor development.
 ...
PMID:Acceleration of age-associated immune decline and mortality by early repeated administration of bestatin to C57BL/6 mice. 348 72

DMN exposure modulates cellular immunity through alterations in the maturation and hematopoiesis of macrophages. DMN-exposed bone marrow stem cells gave rise to increased colony-forming unit-macrophage (CFU-M) colonies while the resulting colonies produced fewer cells/colony. Bone marrow-derived macrophages phenotypically had decreased cells expressing Ia antigens or cells in the S-phase following DMN treatment. Concanavalin A-elicited peritoneal exudate cells from DMN-treated animals demonstrated an increase in the percentage of macrophages and in the number of immature, bi-nucleated cells obtained as well as a concomitant increase in the percentage of Ia antigen-expressing cells. Concanavalin A-elicited peritoneal exudate cells from DMN-exposed animals also had an increased secreted interleukin-1 activity following lipopolysaccharide stimulation without any alteration in the expression of membrane-bound interleukin-1. Thioglycolate-elicited peritoneal exudate cells from DMN-exposed animals demonstrated no changes in cellularity and only showed increases in the percentage of bi-nucleated cells. There were no alterations in the capacity of T cells obtained from DMN-treated animals to respond to either soluble (keyhole limpet hemocyanin) or allo-antigens; nor were there alterations in the capacity of these T cells to either produce or respond to interleukin-2. These findings suggest that the observed DMN-induced modulation(s) in cell-mediated immunity results from changes in macrophage hematopoiesis due to alterations in: the production of regulatory factors controlling their production and/or differentiation or their ability to respond to these factors.
 ...
PMID:Alteration of macrophage differentiation into accessory and effector cells from exposure to dimethylnitrosamine (DMN) in vivo. 349 Apr 56

Neonatal lymphocytes include a subset of E-, OKT3-, OKT4-, OKT8+, HNK-1-, OKM1- cells displaying natural killer (NK) activity. More than 50% of these cells react with the B73.1 monoclonal antibody, moreover most of them bear the DR antigen, the receptor for Peanut agglutinin (PNA) and react with the OKT10 monoclonal antibody. This neonatal subset displays a higher NK activity than unseparated cord blood lymphocytes (CBL) and the present study shows that it is sensitive to boosting effect of IFN-B preincubation. When stimulated with T cell mitogens E-, OKT3-, OKT8+ CBL both produce Interleukin-2 (IL-2) and proliferate. Moreover this neonatal subset produces Interleukin-1 (IL-1) both spontaneously and in response to lipopolysaccharide (LPS). It has been previously suggested that these neonatal cells include a common precursor of NK and T cells. The present study further strengthen this hypothesis.
 ...
PMID:Lymphocyte subpopulations in the neonate: in vitro proliferation, IL-1 and IL-2 production by a subset of HNK-1-, OKT3-, OKT8+ lymphocytes displaying NK activity. 349 66

The time course of immunosuppression induced by acute treatment with O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity in technical formulations of malathion, was examined in female C57B1/6 mice. Both cell-mediated and humoral immune responses were examined and included allospecific cytotoxic T cells, proliferative response to mitogens, interleukin-2 production and antibody production to sheep red blood cells. OOS-TMP pretreatment led to a reversible suppression of the generation of cytotoxic T lymphocytes and antibody-secreting cells to sheep erythrocytes. However, the mitogenic response of splenocytes from animals treated with nontoxic doses of OOS-TMP (as measured by body weight loss, serum cholinesterase levels and splenic lymphocyte number) to concanavalin A was not significantly suppressed, but the response to the B cell mitogen lipopolysaccharide was slightly decreased on day 1 following treatment. In contrast, interleukin-2 production was elevated by 24 h following treatment, but had returned to control levels by day 7. These data suggest that OOS-TMP was able to block the generation of cytotoxic T lymphocytes and antibody responses at doses of OOS-TMP that did not affect body weight or splenic lymphocyte number and this suppression was reversible.
 ...
PMID:Organophosphorus pesticide immunotoxicity: effects of O,O,S-trimethyl phosphorothioate on cellular and humoral immune response systems. 349 28

A subclone, NOB-1, of the mouse EL-4 line constitutively produces very little interleukin-2 but in response to interleukin-1 produces high concentrations of interleukin-2. Co-stimulation with mitogen, phorbol esters or calcium ionophores was not required. NOB-1 is not responsive to tumour necrosis factor alpha, tumour necrosis factor beta, interferon gamma and lipopolysaccharide. The NOB-1 line was used in conjunction with a CTLL line to detect less than 1 pg/ml interleukin-1. Rapid assay was performed by co-culturing the EL-4 cells with CTLL cells. By incorporating a pre-incubation step, followed by thorough washing of the EL-4 cells, responses to interleukin-1 were maintained, but interleukin-2 had no effect. The assay was used to detect interleukin-1 in serum samples and to evaluate neutralizing antisera to interleukin-1.
 ...
PMID:A simple sensitive bioassay for interleukin-1 which is unresponsive to 10(3) U/ml of interleukin-2. 349 88

The mitogenic response of T-cell subsets, the production of interleukin-1 (Il-1) and interleukin-2 (Il-2) and in vitro immunoglobulin production was investigated in patients with Hodgkin's disease (HD). The mitogenic response of mononuclear cells (MNC) and the OKT4+ and OKT8+ subsets was greatly reduced in advanced disease stages and could only partially be restored with exogeneous Il-2. In untreated patients with HD--except those with highly advanced disease--the OKT4+ lymphocytes showed normal response to phytohemagglutinin in contrast to the MNC suggesting inhibiting agents or cells within in the MNC. These findings corresponded to reduced Il-2 synthesis of MNC, whereas isolated OKT4+--cells produced normal or elevated amounts of Il-2. MNC or monocytes produced normal or even higher amounts of lipopolysaccharide-induced Il-1 than controls. The results do not confirm a defect in this component of the interleukin system in HD. The immunological impairment was not limited to the T-cell system but involved B-cell activation and differentiation as well. The pokeweed mitogen-induced IgM, IgG and IgG production was highly suppressed in untreated HD, whereas the MNC of previously treated patients produced subnormal amounts of immunoglobulin in vitro. It is not yet clear whether this defect is T-cell-mediated or primarily a B-cell deficiency.
 ...
PMID:Impaired T- and B-cell functions in patients with Hodgkin's disease. Reduced mitogenic responsibility and Il-2 production is not caused by defective CD4+-cells. 349 58

Poikilotherms are now known to increase their survival by behaviorally induced fevers in response to pathogenic infection. Increased host resistance to viral and bacterial infections has also been noted in homeotherms whose body temperature has been elevated by manipulation of ambient temperature. These observations suggest that fever may increase host resistance by augmenting acquired immunity; thus, this highly conserved response during evolution may provide a survival advantage against environmental pathogens. This possibility has prompted us to investigate the influence of a temperature characteristic of a modest fever in humans (39 degrees C) on T-cell proliferation and function. Our studies revealed that T-cell mitogenesis was enhanced when cultures were incubated at the febrile temperature (39 degrees C). Analysis of T-cell subsets demonstrated that temperature enhanced the mitogenic (Concanavalin A) response of Lyt-1+23- splenocytes; in contrast, hyperthermia was deleterious to lectin-driven proliferation of the Lyt-1-23+ population even in the presence of large quantities of recombinant interleukin-2 (rIL-2). B-cell mitogenesis was invariably inhibited by hyperthermia over a broad range of concentrations of lipopolysaccharide (LPS). Although T-cell mitogenesis was enhanced at the febrile temperature, T-cell proliferation induced by alloantigens or by a murine pathogen, Sendai virus (SV), was diminished at the febrile temperature. Hyperthermia inhibited SV-induced proliferation of Lyt-1+23- lymphocytes, indicating that a febrile temperature can either augment or inhibit T-cell proliferation of the same T-cell subset depending upon the activation signal (i.e., lectin or antigen). Because effector cell development depends upon antigen-induced clonal expansion (proliferation), we evaluated the influence of temperature on primary cytotoxic thymus (T)-derived lymphocyte (CTL) responses against alloantigens and secondary CTL responses against SV under afebrile and febrile conditions. We consistently observed that the induction of alloreactive and virus-specific CTL was diminished in cultures incubated at the elevated temperature, suggesting that a thermosensitive event(s) exists in the progression of CTL derived from either CTL precursors (CTLp) or memory CTL. Furthermore, hyperthermia reduced the number of SV-specific CTL detectable by limiting dilution analysis, suggesting that another event independent of clonal expansion was thermolabile during effector cell development. In view of these results, we suggest that it may be premature to conclude that the observed increase in host resistance induced by a febrile state is mediated by enhanced cell-me
 ...
PMID:Analysis of T-cell subset proliferation at afebrile and febrile temperatures: differential response of Lyt-1+23- lymphocytes to hyperthermia following mitogen and antigen stimulation and its functional consequence on development of cytotoxic lymphocytes. 349 61

Interleukin-2, a product of helper T cells, is essentially involved in the regulation of cell-mediated immunity. Two monocyte-derived factors, interleukin-1 and prostaglandin E2, influence interleukin-2 synthesis with opposite actions. To analyse immunoregulatory function in HBsAg-positive chronic active hepatitis, T cell subsets in peripheral blood and the levels of interleukin-2, interleukin-1 and prostaglandin E2 in supernatants from lectin- or lipopolysaccharide-activated peripheral mononuclear cell cultures were determined in 16 healthy controls and 33 patients with chronic active hepatitis B. Interleukin-2 activity was comparable to the controls in patients without delta infection who had seroconverted to anti-HBe (group 1), but it was significantly reduced in both HBeAg-positive subjects (group 2) (P less than 0.05 vs. controls and group 1) and those cases with positive delta markers (group 3) (P less than 0.01 and less than 0.05 vs. controls and group 1, respectively). In group 3, interleukin-2 was similarly diminished in both anti-HTLV-III-positive and -negative cases as well as in HBeAg- and anti-HBe-positive subjects. Notwithstanding the changes in interleukin-2 activity, no significant differences in the number of T4 cells, or in the levels of either interleukin-1 or prostaglandin E2, were found among the various groups of subjects studied. However, in those groups with reduced interleukin-2 activity an increased number of T8 cells was observed. It is suggested that the low levels of interleukin-2 found in the replicative phase of chronic active hepatitis B and in delta superinfection reflect a disturbed immunoregulation that may contribute to persistent viral replication in these two conditions.
 ...
PMID:Interleukins in chronic active hepatitis B. Relationship with viral markers. 349 50

The antineoplastic drugs Vincristine (VCR) and Vinblastine (VBL) were tested for their effects on Concanavalin A induced Interleukin-2 (IL-2) release by rat splenocytes. Both drugs were found to inhibit IL-2 release in vitro. This effect was noted at doses of 10 ng/ml and 100 ng/ml in case of VBL and at doses of 1 ng/ml, 10 ng/ml and 100 ng/ml with VCR. The in vivo effect of these drugs was studied by injection into rats three days before culture of splenocytes. This also resulted in inhibition of IL-2 release. The effect was manifested with VCR at doses of 0.1 mg/kg bw and 0.5 mg/kg bw and with VBL at 2 mg/kg bw. These drugs were also tested for their effect on Interleukin-1 (IL-1) release by lipopolysaccharide (LPS) stimulated rat peritoneal exudate cells (PEC's) in vitro. No modulation of the production of IL-1 was seen.
 ...
PMID:Inhibition of release of interleukin-2 by vincristine and vinblastine. 350 97


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