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)

Corynebacterium xerosis cell-wall fractions were studied by electron microscopy and analysed for immunomodulating activity. Dramatic splenomegaly occurred following the injection of whole cells or a purified cell-wall fraction (PF), but not with a further purified peptidoglycan (PEP) fraction. Both PF and PEP acted as B-cell mitogens and had adjuvant capabilities comparable to commercial adjuvants. Only the PF fraction enhanced peritoneal natural killer cell (NK) activity, paralleling the splenomegaly response. When spleens from mice injected with PF or PEP were analysed for their abilities to respond to mitogens and for the presence of suppressor cells, reduced mitogenic responses occurred only in PF-injected mice during the peak of splenomegaly. Spleens from both PF- and PEP-injected mice contained suppressor cell activity which peaked 2 weeks post-injection. This activity was primarily directed at B-cell responses to lipopolysaccharide (LPS). C. xerosis cell-wall fractions thus offer great potential as a new immunomodulator.
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PMID:Immunomodulating activities of Corynebacterium xerosis cell-wall fractions. 140 38

Mouse thymectomy at weaning induces a long lasting immunodepression which can be measured by in vivo and in vitro experiments. Lymphocyte proliferation and IL2 production in response to a T cell mitogen are greatly diminished during the whole life of the animals, on the contrary B cell proliferation in the presence of lipopolysaccharide is not modified. The lack of effect of surgery on the in vitro T cytotoxic activity compared to the total abolition of in vivo graft versus host reaction shows that these two phenomena are under the control of different immunocompetent cell subsets. Thymectomy induces a stabilization of natural killer cell activity, while during normal aging, this parameter decreases regularly. Surprisingly, the thy 1+ cell level is normal 8-10 months after thymectomy compared to sham operated animals showing that phenotypically normal cells can be dysfunctional. Macrophage activity is not modified either by aging or by thymectomy. So, thymectomized mice can be used after less than 1 year to study immunopharmacology of aging.
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PMID:Thymectomy at weaning. An accelerated aging model for the mouse immune system. 171 98

We previously demonstrated that the glycol ether 2-methoxyethanol (ME) is immunotoxic in the rat. In this study, the immunotoxicity of 2-methoxyacetic acid (MAA), the principal metabolite of ME, was evaluated in adult male Fischer 344 rats. Rats were dosed by gavage with MAA on 10 consecutive days at dosages ranging from 50 to 200 mg/kg/day. Thymic involution, in the absence of body weight loss, was observed at 100 and 200 mg/kg/day MAA. Lymphoproliferative responses to the mitogens concanavalin A, phytohemagglutinin, and pokeweed mitogen were also reduced at these dosages. The in vitro generated cytotoxic T lymphocyte response was reduced at 200 mg/kg/day MAA. The mixed lymphocyte reaction and natural killer cell activity were unaffected by exposure to MAA. Enumeration of splenic lymphocyte populations revealed a reduction in the percentage of W3/25-positive cells at 100 and 150 mg/kg/day and an increase in the percentage of OX39-positive cells at 200 mg/kg/day; however, no changes in the absolute number of either of these subsets were observed. The plaque forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was suppressed at 50-200 mg/kg/day MAA, while the PFC response to sheep red blood cells (SRBC) was elevated at 50 mg/kg/day. Immunization of rats with TNP-LPS or SRBC followed by oral exposure to MAA at 4 and 28 hr postimmunization resulted in the suppression of the PFC response to TNP-LPS and SRBC at dosages of 100 and 200 mg/kg and 200 and 400 mg/kg, respectively. Equal suppression of the PFC response to TNP-LPS was achieved at equimolar concentrations of ME and MAA. The effects of MAA on the immune system of the rat presented here are very similar to results reported from this lab for ME-induced immune alterations. These results, along with results of experiments in which ME-induced suppression of the PFC response to TNP-LPS was reversed by 4-methylpyrazole, an inhibitor of the oxidation of ME to MAA by alcohol dehydrogenase, indicate that MAA is the proximate immunotoxicant following exposure to the glycol ether 2-methoxyethanol.
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PMID:Evaluation of the immunotoxicity of orally administered 2-methoxyacetic acid in Fischer 344 rats. 177 63

The immunotoxicity of the glycol ether 2-methoxyethanol (ME) was evaluated in adult Fischer 344 rats using a variety of in vitro and in vivo immune function assays. In the first phase of this study, male rats were dosed by oral gavage with ME in water, at dosages ranging from 50 to 200 mg/kg/day, for 10 consecutive days. Decreases in thymus weights were observed at dosages of 50-200 mg/kg/day in the absence of decreased body weights. Lymphoproliferative (LP) responses to concanavalin A and phytohemagglutinin were reduced at 50-200 mg/kg/day while pokeweed mitogen and Salmonella typhimurium mitogen responses were reduced at 200 mg/kg/day. No alterations were observed in natural killer cell activity, mixed lymphocyte reaction, or cytotoxic T lymphocyte responses. The frequency of W3/25-positive splenocytes was reduced in rats dosed at 200 mg/kg/day. Interleukin-2 production was reduced in splenocytes from rats exposed to all dosages of ME. The plaque-forming cell (PFC) response to sheep red blood cells was enhanced in rats dosed at 50 mg/kg/day. However, the PFC response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was suppressed at all dosages. Similarly, the PFC response to TNP-LPS was suppressed in adult female rats dosed with ME. A reduction in the expulsion of adult worms was observed in rats dosed at 200 mg/kg/day that were infected with Trichinella spiralis. A number of male reproductive parameters were also evaluated in rats dosed with ME over 10 days. A significant reduction in testicular weight was observed in rats dosed at 200 mg/kg/day. In the second phase of this study, the PFC response to TNP-LPS was employed to assess the role that metabolism of ME to 2-methoxyacetic acid (MAA) plays in the immunotoxicity of this glycol ether. Ten-day oral dosing with MAA resulted in the inhibition of the PFC response to TNP-LPS at dosages of 50-200 mg/kg/day. Concomitant exposure of rats to ME and the alcohol dehydrogenase inhibitor 4-methylpyrazole blocked ME-induced suppression of this PFC response. Attempts to ameliorate ME-induced suppression of the PFC response with serine, which has been shown to reverse ME-induced developmental and reproductive toxicity, were unsuccessful. These results suggest that the immune system may be more sensitive than the reproductive system to the toxic effects of ME. Furthermore, it appears that MAA is the proximate toxicant for ME-induced alterations in the immune system, as has been demonstrated for ME-induced reproductive and developmental toxicity.
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PMID:Immunotoxicity of 2-methoxyethanol following oral administration in Fischer 344 rats. 185 47

Studies of the effect of short-term, intense treatment with thymic hormone on mitogen response, cytotoxicity to EL-4 lymphoma and natural killer cell (NK) activity was investigated Balb/c nude mice (about 12-16-week-old) were treated 5 times per week for 3 weeks with: Facteur Thymic Serique (FTS) and Thymopentin (TP5, Thymopoietin 32-36) at 1 microgram and 10 ng; TM4 1 ng (an enzyme resistant variant of FTS); Thymosin Fraction V (TF5), 10 and 1 microgram; and 0.1 ml saline, and killed 2 days after the last treatment. The animals were monitored for changes in weight, hematocrit, peripheral blood lymphocyte (PBL) and spleen mitogen response. Additional groups of nude mice were immunized with 1 x 10(7) 5000 R irradiated EL-4 cells 10 days before sacrifice and tested for the presence of cytotoxic T-lymphocytes (CTL). The results show that weight and hematocrit were similar among the groups. Treatment with FTS significantly elevated the number of PBL. Spleen stimulation in mice treated with 1 microgram TP5 was depressed to mitogen concanavalin A (ConA) and lipopolysaccharide (LPS) stimulation. The phytohemagglutinin (PHA) response was not different among the treatment groups. The PBL mitogen response to ConA and LPS was generally increased over saline control in the hormone treated groups but was not statistically significant. The PHA response was only slightly elevated. No CTL was generated in nude mice in any of the groups. However, there was a statistically significant general depression of NK activity in all of the hormone treated animals compared with saline. The results indicate that the basic differentiation defect of the T-cells of nude mice cannot be restored to full functional activity by short-term treatment.
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PMID:Effect of thymic hormone treatment on several immune functions of nude mice. 187 32

Keratinocytes are capable of releasing distinct immunomodulating cytokines such as epidermal cell-derived thymocyte activating factor (ETAF) and an epidermal cell-derived natural killer cell augmenting factor (ENKAF). The present study was performed to determine whether human keratinocytes also may secrete an interleukin 3 (IL-3)-like mediator and thereby participate in the regulation of mast cell activity in the skin. Supernatants of freshly isolated human epidermal cells (EC) and malignant keratinocyte cell lines (A 431, SCC) were tested for their capacity to induce the proliferation of IL-3-dependent cell lines 32 DCL and FDCP. Human epidermal cell interleukin 3 (EC IL-3) is spontaneously released by freshly isolated EC, A 431, and squamous cell carcinoma (SCC) cells. However, both normal EC and A 431 cells produced increased levels of EC IL-3 activity when cultured in the presence of different stimulants, such as phorbol myristate acetate and lipopolysaccharide. The EC IL-3 activity was not inhibited when treated with a monoclonal anti-IL-1 or anti-IL-2-antibody. Biochemical characterization showed that human EC IL-3 has a molecular weight of 17K, elutes of DEAE-ion exchange high-performance liquid chromatography (HPLC) as one major peak at 0.36 M NaCl, and upon HPLC-chromatofocusing exhibits 3 isoelectric points of 7.8, 7.5, and 5.6. Upon reversed-phase HPLC, EC IL-3 activity eluted at about 100% acetonitrile. When highly purified EC IL-3 was labeled with 125I and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a single homogeneous band exhibiting a molecular weight of 17K was seen, which correlated with the IL-3 activity and was free of ETAF/IL-1, IL-2, and interferon activity. These data indicate that human EC synthesize an IL-3-like cytokine which is distinct from ETAF/IL-1, IL-2, and interferon and thereby may participate in the regulation of mast cell activity during inflammatory and fibrotic, as well as hypersensitivity reactions.
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PMID:Human keratinocytes and epidermoid carcinoma cell lines produce a cytokine with interleukin 3-like activity. 243 14

We recently reported on the immunotoxic effects of Aflatoxin B1 (AFB1), a secondary fungal metabolite of Aspergillus flavus in mice. The present paper describes the effect of AFB1 on cellular functions in lymphocytes after in vivo or in vitro exposures. Male BALB/c mice received 0, 0.03, 0.145 or 0.7 mg/kg body weight of AFB1 for 4 weeks. A dose-related decrease in DNA synthesis in lymphocyte cultures with or without the mitogens (lipopolysaccharide, phytohemagglutinin, pokeweed mitogen and concanavalin A) was observed. No effects on protein or ribonucleic acid synthesis were observed. There were dose-dependent decreases in peripheral leucocyte counts and natural killer cell function. Splenic lymphocytes from normal mice cultured with 10(-6) to 10(-4) M AFB1 had decreased DNA synthesis at greater than 1 X 10(-5) M, a decreased protein synthesis at 10(-4) M and decreased RNA synthesis at greater than 2.5 X 10(-5) M. In vitro addition of AFB1 (greater than 50 microM) reduced generation of concanavalin A-induced suppressor cells. The results suggest that AFB1 had a direct and complex effect on lymphocytes and there is a differential sensitivity of various subpopulations.
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PMID:Effects of aflatoxin B1 on murine lymphocytic functions. 249 85

Low doses (50-200 pg or 3.1-12.4 fmol) of interleukin 1 (IL-1) infused into the brain of rats produced rapid suppression of various cellular immune responses in peripheral lymphocytes of rats. Fifteen minutes after infusion of purified IL-1 beta into the lateral ventricle, natural killer cell activity, response to phytohemagglutinin stimulation, and interleukin 2 production were markedly suppressed in lymphocytes isolated from blood and spleen. These effects were due to infusion of IL-1 into brain since they did not occur when IL-1 was infused into the cisterna magna (essentially posterior to brain) or was injected intraperitoneally. Effects of IL-1 in brain could be blocked by simultaneous infusion of alpha-melanocyte-stimulating hormone, which is known to block the biological actions of IL-1. To stimulate release of endogenous IL-1 in brain, lipopolysaccharide was infused; this produced similar effects as IL-1, and these effects also were blocked by alpha-melanocyte-stimulating hormone. At longer intervals after infusion of IL-1 and lipopolysaccharide (3, 6, and 24 hr), immune responses returned to baseline or remained suppressed; i.e., "rebound" immunopotentiation did not occur. Finally, IL-1 infusion suppressed cellular immune responses in adrenalectomized animals, thereby showing that the effects of central IL-1 on peripheral cellular immune responses were, at least in part, independent of the stimulatory effect of IL-1 on secretion of adrenal hormones. These results indicate a link from brain to peripheral immune responses by means of action of a cytokine acting in the brain.
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PMID:Intracerebroventricular infusion of interleukin 1 rapidly decreases peripheral cellular immune responses. 254 13

We have previously shown that depletion of central nervous system (CNS) catecholamines by injecting the neurotoxin 6-hydroxydopamine (6-OHDA) into the cisterna magna of C57B1/6 mice markedly impairs the humoral immune response to sheep red blood cells. This work extends these observations by showing that 6-OHDA treatment also inhibits the humoral antibody response to the T-cell-dependent antigen trinitrophenyl-keyhole limpet hemocyanin, but does not affect the response to the T-independent antigen trinitrophenyl-lipopolysaccharide. This treatment also impairs humoral responsiveness at peripheral lymphoid sites in addition to inhibiting natural killer cell activity. However, 6-OHDA treatment in vivo does not affect in vitro mixed lymphocyte responsiveness, mitogen-induced lymphocyte activation or antigen presentation by macrophages.
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PMID:Central catecholamine depletion impairs in vivo immunity but not in vitro lymphocyte activation. 326 Sep 5

Analogues that are poor substrates for adenosine deaminase or purine nucleoside phosphorylase may mimic immunodeficiencies associated with the enzyme deficiencies, and their activities may be directed toward selected lymphocyte subpopulations. Four analogues were studied for their effects on primary antibody response to either a T-dependent (sheep erythrocytes) or T-independent (trinitrophenyl-conjugated Escherichia coli lipopolysaccharide) antigen as well as effects on T-cytotoxic and natural killer cell activities in mice. The nucleosides were: an adenosine analogue, tubercidin; two deoxyadenosine analogues, 2-chloro, 2'-deoxyadenosine and 2-fluoroadenine arabinoside-5'-phosphate; and a deoxyguanosine analogue, 9-beta-D-arabinosylguanine. Drugs were given i.p. once daily for 3 consecutive days. Immune responses were determined in spleen cell suspensions 1 day after the last dose. Tubercidin inhibited both T-cytotoxic and natural killer cell activities at doses that did not reduce primary antibody response, whereas the reverse was true for 2-chloro, 2'-deoxyadenosine and 2-fluoroadenine arabinoside-5'-phosphate. At higher doses, T-cytotoxic lymphocytes appeared to be more sensitive than natural killer cells to the deoxyadenosine analogues. 9-beta-D-Arabinosylguanine did not selectively inhibit the immune responses at doses that clearly reduced the yield of spleen lymphocytes. Assuming the analogues mimic endogenous nucleosides, the results suggest that natural killer cells are more sensitive to adenosine than are those cells responsible for primary antibody response, whereas the reverse is true for deoxyadenosine.
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PMID:Selective modulation of antibody response and natural killer cell activity by purine nucleoside analogues. 326 25


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