Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RRR-alpha-tocopheryl succinate was demonstrated to be a potent in vitro modulator of retrovirus-induced immune abnormalities. Spleen cells from avian erythroblastosis virus (AEV)-infected chickens exhibit suppressed T cell mitogen-induced proliferative responses and elevated levels of suppressor T cell activity. In vitro addition of RRR-alpha-tocopheryl succinate resulted in amelioration of these abnormalities. Antioxidants including Trolox (a water-soluble analogue of RRR-alpha-tocopherol with antioxidant properties) and a combination of butylated hydroxyanisole and butylated hydroxytoluene were able to restore immune functions to levels similar to those achieved with RRR-alpha-tocopheryl succinate treatment. Aspirin, an irreversible inhibitor of cyclooxygenase activity, was capable of ameliorating some of the AEV-induced immune dysfunctions. These studies suggest a role for the antioxidant functions of RRR-alpha-tocopheryl succinate in modulation of retrovirus-induced immune abnormalities.
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PMID:RRR-alpha-tocopheryl succinate enhances T cell mitogen-induced proliferation and reduces suppressor activity in spleen cells derived from AEV-infected chickens. 182 13

The number of spontaneous lung metastases and the frequency of metastasis formation in the lymph nodes of mice were studied following the induction of tumour growth by injection of tumour cells. A syngeneic transplantable mammary adenocarcinoma, MMT 1, from C3H/He mice, and a cloned strain, MMTV4, obtained by treating MMT1 cells with 5-azacytidine in vitro, were used. No differences between MMT1 and MMTV4 were detected in the number of spontaneous metastases in the lungs of mice. An in vitro cytotoxic test and an adoptive transfer test were used to measure cytotoxic activity and the antimetastatic activity of spleen macrophages. The macrophages from mice bearing the MMT1 tumour exhibited antimetastatic activity in the adoptive transfer test, and specific and nonspecific cytotoxic activity in the in vitro test. Macrophages from mice carrying the MMTV4 tumour possessed nonspecific cytotoxic activity in vitro but did not exhibit antimetastatic activity in the adoptive transfer test. Tumours were surgically removed 13-15 days after their induction. Two weeks after the MMT1 tumour was resected, an abrupt increase in the number of spontaneous metastases in the lungs and in the lymph nodes was observed, whereas after removal of the MMTV4 tumour there were no changes in the number of lung metastases. When mice with the MMT1 tumour were given the cyclooxygenase inhibitor, indomethacin, in their drinking water, there was a significant decrease in the number of spontaneous lung metastases. Spleen macrophages from mice operated on after injection with MMT1 or MMTV4 did not possess specific cytotoxicity in the in vitro test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Participation of macrophages in the mechanism mediating the enhancement of metastasis formation after tumour resection. 184 24

This study examined the metabolism of arachidonic acid (20:4) by splenic mononuclear cells from BALB/c mice infected with Leishmania donovani. Spleen cells removed from mice after either 4 or 8 weeks of infection and cultured in the presence of phytohemagglutinin (PHA) incorporated 60-70% less [3H]thymidine and synthesized 2- to 5-fold more prostaglandin E2 than did spleen cells from normal mice. Inhibition of cyclooxygenation by sodium meclofenamate was associated with restoration of PHA-induced spleen cell blastogenesis. Thin-layer chromatography of spleen cell extracts showed that PHA-stimulated spleen cells from infected animals synthesized 54 and 27% more 5-hydroxyeicosatetraenoic acid (5-HETE) and 12/15-HETE respectively, when compared to spleen cells from noninfected mice. Culture medium of spleen cells from infected mice also contained 25% more immunoreactive leukotriene C4. Nordihydroguaiaretic acid (3 microM) reduced spleen cell synthesis of 12/15-HETE while minimally affecting 5-HETE production. These data indicated that increased cyclooxygenase and lipoxygenase activities in spleen cells from mice infected with L. donovani resulted in the generation of 20:4 metabolites with the capability of altering T-lymphocyte function.
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PMID:Arachidonic acid metabolism in murine leishmaniasis (Donovani): ex-vivo evidence for increased cyclooxygenase and 5-lipoxygenase activity in spleen cells. 643 88

Tumor necrosis factor (TNF) is considered to be deeply involved in the hepatocyte damages in severe hepatitis. To delineate which mediators are involved in the production of TNF in vivo, we examined regulatory mechanisms of the production of TNF by rat Kupffer cells using a variety of mediators. Lipopolysaccharide (LPS) markedly induced TNF production by Kupffer cells. Kinetic studies revealed a rapid release of TNF within 3-4 hrs after the addition of LPS to the culture medium. Spleen cell derived-macrophage activating factor prepared from rat spleen cells did not by itself induce the production of TNF. However, the presence of a small amount of the factor during or before exposure to LPS induced higher levels of TNF, suggesting that macrophage activating factor had a priming effect. Recombinant human interferon-gamma and recombinant human granulocyte-macrophage colony stimulating factor, the natural types of which are components of the macrophage activating factor, displayed similar effects. Prostaglandin E2 (PGE2) and dexamethasone both inhibited LPS-induced TNF production in a dose dependent manner. Indomethacin, a cyclooxygenase inhibitor, increased LPS-induced TNF production. Interestingly, a combination of PGE2 and indomethacin inhibited TNF production more strongly than PGE2 alone, suggesting that the simultaneous treatment with PGE2 and indomethacin decreases liver damage in severe hepatitis rather than PGE2 alone. In addition, PGE2 pretreatment reduced the response to the newly added PGE2, suggesting the presence of a desensitization mechanism in the PGE2 receptor system. These findings suggest that spleen cell-derived macrophage activating factor and bowel-derived LPS take important parts in TNF production through the portal blood in the liver in vivo.
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PMID:Tumor necrosis factor production by rat Kupffer cells-regulation by lipopolysaccharide, macrophage activating factor and prostaglandin E2. 1033 31

The potential health effects of inhaling carbon nanotubes are important because of possible exposures in occupational settings. Previously, we have shown mice that have inhaled multiwalled carbon nanotubes have suppressed systemic immune function. Here, we show the mechanisms for this immune suppression. Mice were exposed to 0, 0.3 or 1 mg m(-3) multiwalled carbon nanotubes for 6 h per day for 14 consecutive days in whole-body inhalation chambers. Only those exposed to a dose of 1 mg m(-3) presented suppressed immune function; this involved activation of cyclooxygenase enzymes in the spleen in response to a signal from the lungs. Spleen cells from exposed animals partially recovered their immune function when treated with ibuprofen, a drug that blocks the formation of cyclooxygenase enzymes. Knockout mice without cyclooxygenase enzymes were not affected when exposed to multiwalled carbon nanotubes, further confirming the importance of this enzyme in suppression. Proteins from the lungs of exposed mice suppressed the immune function of spleen cells from normal mice, but not those from knockout mice. Our findings suggest that signals from the lung can activate signals in the spleen to suppress the immune function of exposed mice.
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PMID:Mechanisms for how inhaled multiwalled carbon nanotubes suppress systemic immune function in mice. 1958 90