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Sample records for spleen cells induced

  1. The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury

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    Mandal, Mili; Gardner, Carol R.; Sun, Richard; Choi, Hyejeong; Lad, Sonali; Mishin, Vladimir; Laskin, Jeffrey D.; Laskin, Debra L.

    2016-01-01

    Macrophages have been shown to play a role in acetaminophen (APAP)-induced hepatotoxicity, contributing to both pro- and anti-inflammatory processes. In these studies, we analyzed the role of the spleen as an extramedullary source of hepatic macrophages. APAP administration (300 mg/kg, i.p.) to control mice resulted in an increase in CD11b + infiltrating Ly6G + granulocytic and Ly6G − monocytic cells in the spleen and the liver. The majority of the Ly6G + cells were also positive for the monocyte/macrophage activation marker, Ly6C, suggesting a myeloid derived suppressor cell (MDSC) phenotype. By comparison, Ly6G − cells consisted of 3 subpopulations expressing high, intermediate, and low levels of Ly6C. Splenectomy was associated with increases in mature (F4/80 + ) and immature (F4/80 − ) pro-inflammatory Ly6C hi macrophages and mature anti-inflammatory (Ly6C lo ) macrophages in the liver after APAP; increases in MDSCs were also noted in the livers of splenectomized (SPX) mice after APAP. This was associated with increases in APAP-induced expression of chemokine receptors regulating pro-inflammatory (CCR2) and anti-inflammatory (CX3CR1) macrophage trafficking. In contrast, APAP-induced increases in pro-inflammatory galectin-3 + macrophages were blunted in livers of SPX mice relative to control mice, along with hepatic expression of TNF-α, as well as the anti-inflammatory macrophage markers, FIZZ-1 and YM-1. These data demonstrate that multiple subpopulations of pro- and anti-inflammatory cells respond to APAP-induced injury, and that these cells originate from distinct hematopoietic reservoirs. - Highlights: • Multiple inflammatory cell subpopulations accumulate in the spleen and liver following acetaminophen (APAP) intoxication. • Splenectomy alters liver inflammatory cell populations responding to APAP. • Inflammatory cells accumulating in the liver in response to APAP originate from the spleen and the bone marrow. • Hepatotoxicity is reduced in

  2. The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury

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    Mandal, Mili, E-mail: milimandal@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Gardner, Carol R., E-mail: cgardner@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sun, Richard, E-mail: fishpower52@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Choi, Hyejeong, E-mail: choi@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Lad, Sonali, E-mail: sonurose92@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Mishin, Vladimir, E-mail: mishinv@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2016-08-01

    Macrophages have been shown to play a role in acetaminophen (APAP)-induced hepatotoxicity, contributing to both pro- and anti-inflammatory processes. In these studies, we analyzed the role of the spleen as an extramedullary source of hepatic macrophages. APAP administration (300 mg/kg, i.p.) to control mice resulted in an increase in CD11b{sup +} infiltrating Ly6G{sup +} granulocytic and Ly6G{sup −} monocytic cells in the spleen and the liver. The majority of the Ly6G{sup +} cells were also positive for the monocyte/macrophage activation marker, Ly6C, suggesting a myeloid derived suppressor cell (MDSC) phenotype. By comparison, Ly6G{sup −} cells consisted of 3 subpopulations expressing high, intermediate, and low levels of Ly6C. Splenectomy was associated with increases in mature (F4/80{sup +}) and immature (F4/80{sup −}) pro-inflammatory Ly6C{sup hi} macrophages and mature anti-inflammatory (Ly6C{sup lo}) macrophages in the liver after APAP; increases in MDSCs were also noted in the livers of splenectomized (SPX) mice after APAP. This was associated with increases in APAP-induced expression of chemokine receptors regulating pro-inflammatory (CCR2) and anti-inflammatory (CX3CR1) macrophage trafficking. In contrast, APAP-induced increases in pro-inflammatory galectin-3{sup +} macrophages were blunted in livers of SPX mice relative to control mice, along with hepatic expression of TNF-α, as well as the anti-inflammatory macrophage markers, FIZZ-1 and YM-1. These data demonstrate that multiple subpopulations of pro- and anti-inflammatory cells respond to APAP-induced injury, and that these cells originate from distinct hematopoietic reservoirs. - Highlights: • Multiple inflammatory cell subpopulations accumulate in the spleen and liver following acetaminophen (APAP) intoxication. • Splenectomy alters liver inflammatory cell populations responding to APAP. • Inflammatory cells accumulating in the liver in response to APAP originate from the spleen and the

  3. Copper-induced immunotoxicity involves cell cycle arrest and cell death in the spleen and thymus

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    Mitra, Soham; Keswani, Tarun; Dey, Manali; Bhattacharya, Shaswati; Sarkar, Samrat; Goswami, Suranjana; Ghosh, Nabanita; Dutta, Anuradha; Bhattacharyya, Arindam

    2012-01-01

    Copper is an essential trace element for human physiological processes. To evaluate the potential adverse health impact/immunotoxicological effects of this metal in situ due to over exposure, Swiss albino mice were treated (via intraperitoneal injections) with copper (II) chloride (copper chloride) at doses of 0, 5, or 7.5 mg copper chloride/kg body weight (b.w.) twice a week for 4 wk; these values were derived from LD 50 studies using copper chloride doses that ranged from 0 to 40 mg/kg BW (2×/wk, for 4 wk). Copper treated mice evidenced immunotoxicity as indicated by dose-related decreases and increases, respectively, in thymic and splenic weights. Histomorphological changes evidenced in these organs were thymic atrophy, white pulp shrinkage in the spleen, and apoptosis of splenocytes and thymocytes; these observations were confirmed by microscopic analyses. Cell count analyses indicated that the proliferative functions of the splenocytes and thymocytes were also altered because of the copper exposures. Among both cell types from the copper treated hosts, flow cytometric analyses revealed a dose related increase in the percentages of cells in the Sub-G 0 /G 1 state, indicative of apoptosis which was further confirmed by Annexin V binding assay. In addition, the copper treatments altered the expression of selected cell death related genes such as EndoG and Bax in a dose related manner. Immunohistochemical analyses revealed that there was also increased ubiquitin expression in both the cell types. In conclusion, these studies show that sublethal exposure to copper (as copper chloride) induces toxicity in the thymus and spleen, and increased Sub G 0 /G 1 population among splenocytes and thymocytes that is mediated, in part, by the EndoG–Bax–ubiquitin pathway. This latter damage to these cells that reside in critical immune system organs are likely to be important contributing factors underlying the immunosuppression that has been documented by other

  4. Disorder of G2-M Checkpoint Control in Aniline-Induced Cell Proliferation in Rat Spleen.

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    Jianling Wang

    Full Text Available Aniline, a toxic aromatic amine, is known to cause hemopoietic toxicity both in humans and animals. Aniline exposure also leads to toxic response in spleen which is characterized by splenomegaly, hyperplasia, fibrosis and the eventual formation of tumors on chronic in vivo exposure. Previously, we have shown that aniline exposure leads to iron overload, oxidative DNA damage, and increased cell proliferation, which could eventually contribute to a tumorigenic response in the spleen. Despite our demonstration that cell proliferation was associated with deregulation of G1 phase cyclins and increased expression of G1 phase cyclin-dependent kinases (CDKs, molecular mechanisms, especially the regulation of G2 phase and contribution of epigenetic mechanisms in aniline-induced splenic cellular proliferation remain largely unclear. This study therefore, mainly focused on the regulation of G2 phase in an animal model preceding a tumorigenic response. Male Sprague-Dawley rats were given aniline (0.5 mmol/kg/day in drinking water or drinking water only (controls for 30 days, and expression of G2 phase cyclins, CDK1, CDK inhibitors and miRNAs were measured in the spleen. Aniline treatment resulted in significant increases in cell cycle regulatory proteins, including cyclins A, B and CDK1, particularly phosphor-CDK1, and decreases in CDK inhibitors p21 and p27, which could promote the splenocytes to go through G2/M transition. Our data also showed upregulation of tumor markers Trx-1 and Ref-1 in rats treated with aniline. More importantly, we observed lower expression of miRNAs including Let-7a, miR-15b, miR24, miR-100 and miR-125, and greater expression of CDK inhibitor regulatory miRNAs such as miR-181a, miR-221 and miR-222 in the spleens of aniline-treated animals. Our findings suggest that significant increases in the expression of cyclins, CDK1 and aberrant regulation of miRNAs could lead to an accelerated G2/M transition of the splenocytes, and

  5. Concanavalin A-induced and spontaneous suppressor cell activities in peripheral blood lymphocytes and spleen cells from gastric cancer patients.

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    Toge, T; Hamamoto, S; Itagaki, E; Yajima, K; Tanada, M; Nakane, H; Kohno, H; Nakanishi, K; Hattori, T

    1983-11-01

    In 173 gastric cancer patients, activities of Concanavalin-A-induced suppressor cells (Con-AS) and spontaneous suppressor cells (SpS) in peripheral blood lymphocytes (PBL), splenic vein lymphocytes (SVL), and spleen cells (SCs) were investigated. Suppressions by Con-AS in PBL were significantly effective in patients of Stages III and IV, while suppressions by SpS were effective in patients with recurrent tumors. Thus, in PBLs of cancer patients, suppressor precursors, which are considered to be activated in vitro by Concanavalin-A, seemed to appear with the advances of the disease, and SpS activities, which could be already activated in vivo, seemed to increase in the terminal stage. In SCs, increased activities of Con-AS, but normal activities of SpS, were observed, and these suppressor-cell populations consisted of glass nonadherent cells. Suppressor activities of SCs would be due to suppressor T-cells, not to other types of cells. Furthermore, Con-AS existed in the medium-sized lymphocytes, which were fractionated on the basis of cell size, while SpS in the large-sized lymphocytes. A higher proportion of T-cells, bearing Fc receptors for IgG, was observed in the larger-sized lymphocyte fractions. Cell numbers in the large-sized lymphocyte fraction tended to increase with the advances of tumors. From these results, it is suggested that higher presence of suppressor precursors and the increase of SpS activities may occur in cancer patients, depending on the tumor advancing.

  6. X-ray-induced production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by mouse spleen cells in culture

    International Nuclear Information System (INIS)

    Onoda, M.; Shinoda, M.; Tsuneoka, K.; Shikita, M.

    1980-01-01

    Spleen cells were collected from normal mice and cultured in a medium containing 20% calf serum. Addition of lipopolysaccharide (LPS) in the culture significantly increased the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), and a maximum induction was attained in 5 days. Irradiation of the spleen cells with 300 to 3000 R x rays also enhanced the production of GM-CSF, but there was a latent period of about 5 days before the factor appeared in the culture medium. The observed difference between LPS and x rays in the timing of inducing GM-CSF production in the spleen cell culture was consistent with the difference observed in animals. These results suggest that different mechanisms of GM-CSF production operate in the spleen in response to either LPS or x rays

  7. Influence of some radioprotective and radiosensitizing compounds on the replicative and repair induced DNA synthesis of rats spleen cells in vitro

    International Nuclear Information System (INIS)

    Goette, A.

    1982-01-01

    The effect of cysteine, dithiothreitol, N-ethylmaleimide, cytosinearabinoside, ethidiumbromide, bleomycine and diethyldithiocarbamate on the replicative and repair induced DNA synthesis in vitro was tested by using rats spleen cells. Besides the incorporation of a labeled DNA precursor (TdR- 3 H) the sedimentation of DNA in sucrose gradients was inquired. With respect to the DNA synthesis an uniform mechanism of action for the radioprotective substances can't be seen. Thymocytes and spleen cells seem to possess different systems of repair; this may be an explanation for their different sensibility against ionizing radiation. (orig./MG) [de

  8. Measurement of DNA breakage and breakage repair in mice spleen cells induced by ionizing radiation

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    Wang Qin; Xue Jingying; Li Jin; Mu Chuanjie; Fan Feiyue

    2007-01-01

    Objective: To investigate the radioresistance mechanism of IBM-2 mice through measuring DNA single-strand break(SSB) and double-strands break (DSB) as well as their repair. Methods: Pulsed-field gel electrophoresis was used to measure DSB and SSB in IRM-2 mice and their parental mice ICR/JCL and 615 mice after exposure to different doses of γ-ray at different postirradiation time. Results: The initial DNA damages, ie the quantities of DSB and SSB in unirradiation IRM-2 mice were less serious than that of their parental mice ICR/JCL and 615 alice(P<0.01). The percent- age of DSB and SSB in IBM -2 mice was significantly lower than that of ICB/JCL and 615 mice after exposure to various doses of γ-ray(P<0.01 and P<0.05). There were not statistic differences in DSB and SSB repair between IRM-2 mice and their parental mice after exposure to 2Gy radiation. The DNA damage repair rate induced by 4Gy and 8Gy radiation in IRM - 2 mice was rapid, ie the repair rate of SSB and DSB after 0.5h and 1h postirradiation in IRM-2 mice was higher than that of their' parental mice (P<0.01 and P<0.05). And remaining damages after repair in IRM-2 mice were lower than that of ICR/JCL and 615 mice. Conclusion: The DNA damages in IBM-2 mice were lower than that of their parental mice after exposure to ionizing radiation. Moreover, the repair rate of SSB and DSB was higher than that of their parental mice, which perhaps were the radioresistance causes of IBM-2 mice. Therefore IRM-2 mice are naturally resistant to DNA damages induced by ionizing radiation. (authors)

  9. Thymosin alpha 1 (Ta-1) induction of spleen cell proliferation and production of interleukin 2 (IL2) after irradiation-induced depression of systematic cellular immunity (SCI)

    International Nuclear Information System (INIS)

    Gray, W.C.; Revie, D.R.; Oliver, J.H.; Hasslinger, B.J.; Suter, C.M.; Blanchard, C.L.; Goldstein, A.L.; Chretien, P.B.

    1986-01-01

    To assess the effects of Ta-1 on recovery from irradiation induced depression of SCI, C3H mice were given 400 rads (240kV) on each of 3 alternate days via head, chest and pelvic portals and assays performed 2 days after the last exposure. Compared with shams, total spleen cell counts and production of IL2, total peripheral blood lymphocyte and T-cell levels, and delayed type hypersensitivity to oxazolone (DTH-O) were all similarly depressed in the three portal groups (p < .0001). Following optimum doses of Ta-1, administered daily starting with the first day of irradiation, DTH-O in the head and chest groups was restored, but in the pelvic group was only partially corrected. Changes in total spleen cell counts and IL2 production paralleled and covaried with DTH-O (p < .0001). The results offer IL2 induced lymphocyte proliferation as a reparative mechanism after radiation-induced depression of SCI. The incomplete restoration of SCI in the pelvic group suggests that generation of IL2-producing spleen cells by Ta-1 requires pelvic and other bone marrow lymphocyte precursors

  10. BAFF induces spleen CD4+ T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

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    Ji, Fang; Chen, Rongjing; Liu, Baojun; Zhang, Xiaoping; Han, Junli; Wang, Haining; Shen, Gang; Tao, Jiang

    2012-01-01

    Highlights: ► Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4 + T cells. ► Carrying out siRNA technology to study FOXO3A protein function. ► Helpful to understand the T cell especially CD4 + T cell‘s role in immunological reaction. -- Abstract: The TNF ligand family member “B cell-activating factor belonging to the TNF family” (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4 + spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4 + T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4 + spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4 + T cell proliferation.

  11. BAFF induces spleen CD4{sup +} T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

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    Ji, Fang; Chen, Rongjing [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Liu, Baojun [Laboratory of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai (China); Zhang, Xiaoping [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Han, Junli; Wang, Haining [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Shen, Gang [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Tao, Jiang, E-mail: taojiang2012@yahoo.cn [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4{sup +} T cells. Black-Right-Pointing-Pointer Carrying out siRNA technology to study FOXO3A protein function. Black-Right-Pointing-Pointer Helpful to understand the T cell especially CD4{sup +} T cell's role in immunological reaction. -- Abstract: The TNF ligand family member 'B cell-activating factor belonging to the TNF family' (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4{sup +} spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4{sup +} T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4{sup +} spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4{sup +} T cell proliferation.

  12. Calf Spleen Extractive Injection (CSEI, a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway

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    Dongxu Jia

    2016-10-01

    Full Text Available Calf Spleen Extractive Injection (CSEI, a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation. CSEI significantly inhibited HepG2-xenografted tumor growth in nude mice. In cell and animal experiments, CSEI increased the activations of pro-apoptotic proteins including caspase 8, caspase 9 and caspase 3; meanwhile, it suppressed the expressions of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2 and anti-oxidation proteins, such as nuclear factor-erythroid 2 related factor 2 (Nrf2 and catalase (CAT. The enhanced phosphorylation of P38 and c-JunN-terminalkinase (JNK, and decreased phosphorylation of extra cellular signal-regulated protein kinase (ERKs were observed in CSEI-treated cells and tumor tissues. CSEI-induced cell viability reduction was significantly attenuated by N-Acetyl-l-cysteine (a ROS inhibitor pretreatment. All data demonstrated that the upregulated oxidative stress status and the altered mitogen-activated protein kinases (MAPKs phosphorylation contributed to CSEI-driven mitochondrial dysfunction. Taken together, CSEI exactly induced apoptosis in human hepatocellular carcinoma cells via ROS/MAPKs dependent mitochondrial pathway.

  13. Spleen

    International Nuclear Information System (INIS)

    Mittelstaedt, C.A.; McCartney, W.H.; Mauro, M.A.; Vincent, L.M.; Peterson, N.P.; Staab, E.V.

    1984-01-01

    Imaging modalities currently available for the evaluation of splenic disorders include /sup 99m/Tc-sulfur colloid (TcSC) radionuclide splenic scintigraphy, ultrasound, and computed tomography (CT). These techniques produce images of the spleen on the basis of reticuloendothelial function, echogenic properties, and x-ray attenuation, respectively. No one technique is clearly superior to another for all clinical situations or disease processes. Each modality has its strengths and limitations that relate to the properties being measured (function, echogenicity, attenuation) and the disease processes involving the spleen. This chapter offers a combined approach to splenic imaging in the evaluation of focal disease, diffuse disease, traumatic disorders, normal variations, congenital anomalies, and perisplenic disorders

  14. Role of the spleen in cyclophosphamide-induced hematosuppression and extramedullary hematopoiesis in mice.

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    Wang, Yuli; Meng, Qinggang; Qiao, Haiquan; Jiang, Hongchi; Sun, Xueying

    2009-05-01

    Extramedullary hematopoiesis (EMH) is induced in spleens due to various diseases. The aim of this study is to investigate the role of spleen in cyclophosphamide (CTX)-induced hematosuppression and EMH in mice. Balb/c mice were IP injected with 300 mg/kg CTX 2 weeks after splenectomy or sham operation and randomly sacrificed 1, 3, 7, 14, and 21 days after injection. Blood samples were collected, and spleens were weighed, histologically analyzed, and then used for flow cytometry. There were significant differences in white blood count, red blood count, platelet numbers and hemoglobin concentration between the splenectomized and sham-operated mice after CTX injection. The cellularity of the spleen was reduced 3 days following CTX treatment but then rose 7 days after CTX treatment. The numbers of colony-forming units in the spleen reached a peak 7 days after CTX injection, then declined. Flow cytometry demonstrated the percentage of CD34(+) and CD117(+) cells in the spleen increased 7 days after CTX injection, indicating the hematopoietic stem and progenitor cells in the spleen. The study indicates that EMH occurs as a compensatory reaction to CTX-induced hematosuppression in the murine spleen, implying that conservation of the spleen may promote the recovery of cancer patients from chemotherapy-induced hematosuppression.

  15. Arsenic interferes with the signaling transduction pathway of T cell receptor activation by increasing basal and induced phosphorylation of Lck and Fyn in spleen cells

    International Nuclear Information System (INIS)

    Soto-Pena, Gerson A.; Vega, Libia

    2008-01-01

    Arsenic is known to produce inhibition as well as induction of immune cells proliferative responses depending on the doses as one of its mechanisms of immunotoxicity. Here we evaluate the effect of arsenic exposure on the activation of splenic mononuclear cells (SMC) in male CD57BL6N mice. Intra-gastric exposure to arsenic (as sodium arsenite) for 30 days (1, 0.1, or 0.01 mg/kg/day), reduced the proportion of CD4+ cells and the CD4+/CD8+ ratio in the spleen, increasing the proportion of CD11b+ cells. Arsenic exposure did not modify the proportion of B cells. SMC showed an increased level of phosphorylation of lck and fyn kinases (first kinases associated to TCR complex when activated). Although normal levels of apoptosis were observed on freshly isolated SMC, an increase in apoptotic cells related with the increase in phosphorylation of lck and fyn was observed when SMC were activated with Concanavalin-A (Con-A). Arsenic exposure reduced the proliferative response of SMC to Con-A, and also reduced secretion of IL-2, IL-6, IL-12 and IFNγ. No effect was observed on IL-4, and IL-10 secretion. The same effects were observed when SMC of exposed animals were activated with anti-CD3/CD28 antibodies for 24 h, but these effects were transitory since a recovery, up to control levels or even higher, were observed after 72 h of stimulation. This study demonstrates that repeated and prolonged exposure to arsenic alters cell populations and produces functional changes depending on the specific activation pathway, and could be related with the phosphorylation status of lck and fyn kinases

  16. Enhanced gamma interferon responses of mouse spleen cells following immunotherapy for tuberculosis relapse.

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    Gil, Olga; Vilaplana, Cristina; Guirado, Evelyn; Díaz, Jorge; Cáceres, Neus; Singh, Mahavir; Cardona, Pere-Joan

    2008-11-01

    Gamma interferon responses of spleen cells in mice were examined during postchemotherapy relapse of intraperitoneally induced latent tuberculous infection. The mycobacterial extract RUTI, which prevented the relapse, significantly enhanced the immune responses to secreted and structural recombinant mycobacterial antigens, suggesting that RUTI-mediated protection was mediated by activated T cells.

  17. The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.

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    Takeshi Itoh

    Full Text Available Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV, beneath the kidney capsule (KC, or into the spleen (SP. The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05. Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.

  18. Increased DNA-repair in spleen cells of M. Hodgkin

    International Nuclear Information System (INIS)

    Frischauf, H.; Neumann, E.; Howanietz, L.; Dolejs, I.; Tuschl, H.; Altmann, H.

    1974-11-01

    In spleen cells of control patients and cells of Morbus Hodgkin, DNA-repair after gamma- and UV-irradiation was determined measuring the incorporated 3H-thymidine activity in the DNA. Additionally, the ratio of labeled cells compared to non-labeled cells and the grains per cell were evaluated by autoradiographic investigations. DNA-content per cell was measured using pulsecytophotometry. A significant increase of DNA-repair capacity after gamma-irradiation was found by density gradient centrifugation in alkaline sucrose. The same trend could be shown by investigations of unscheduled DNA-synthesis using autoradiographic method. (author)

  19. Activation of spleen cells by ArtinM may account for its immunomodulatory properties.

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    Silva, Thiago Aparecido da; Souza, Maria Aparecida de; Cecílio, Nerry Tatiana; Roque-Barreira, Maria Cristina

    2014-09-01

    ArtinM is a D-mannose-binding lectin extracted from Artocarpus heterophyllus that promotes interleukin-12 production by macrophages and dendritic cells. This property is considered responsible for T helper 1 immunity induced in vivo after ArtinM administration. In this study, we investigated the effect of native (jArtinM) and recombinant (rArtinM) forms of lectin on murine spleen cells and isolated T lymphocytes. We found that ArtinM binds to the surface of spleen cells. This interaction, which was blocked by D-mannose, induced cell activation, as manifested by increased mitochondrial activity, interleukin-2 production, and cell proliferation. We verified that a 30-times higher concentration of rArtinM was required to trigger optimal activation of spleen cells compared with that needed with jArtinM, although these proteins have identical sugar recognition properties and use the same signaling molecules to trigger cell activation. Because the distinction between native and recombinant is restricted to their tertiary structure (tetrameric and monomeric, respectively), we postulated that the multi-valence of jArtinM accounts for its superiority in promoting clustering of cell surface glycoreceptors and activation. The jArtinM and rArtinM activation effect exerted on spleen cells was reproduced on purified CD4(+) T cells. Our results suggest that ArtinM interaction with T cells leads to responses that may act in concert with the interleukin-12 produced by antigen-presenting cells to modulate immunity toward the T helper 1 axis. Further studies are necessary to dissect ArtinM/T-cell interactions to more fully understand the immunomodulation induced by carbohydrate recognition.

  20. Spleen removal

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    ... spleen. Sickle cell anemia . Splenic artery aneurysm (rare). Trauma to the spleen. Risks Risks for anesthesia and surgery in general ... removal - series References Brandow AM, Camitta BM. Hyposplenism, splenic trauma, and splenectomy. In: Kliegman RM, Stanton BF, St. ...

  1. Unscheduled DNA synthesis in spleen cells of mice exposed to low doses of total body irradiation

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.; Hruby, E.

    1983-07-01

    Unscheduled DNA synthesis was induced by UV irradiation of spleen cells obtained from C 57 Bl mice after repeated total body irradiation of 0.05 Gy 60 Co (0.00125 Gy/mice) and determined autoradiographically. An enhancement in the ability for repair of UV induced DNA lesions was observed in cells of gamma irradiated animals. While the amount of 3 H-thymidine incorporated per cell was increased, the percentage of labeled cells remained unchanged. The present results are compared with previous data on low dose radiation exposure in men. (Author) [de

  2. Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its amelioration by carnosine.

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    Banerjee, Sharmistha; Sinha, Krishnendu; Chowdhury, Sayantani; Sil, Parames C

    2018-01-05

    cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Premalignant lesions skew spleen cell responses to immune modulation by adipocytes.

    Science.gov (United States)

    Vielma, Silvana A; Klein, Richard L; Levingston, Corinne A; Young, M Rita I

    2013-05-01

    Obesity can promote a chronic inflammatory state and is associated with an increased risk for cancer. Since adipocytes can produce mediators that can regulate conventional immune cells, this study sought to determine if the presence of premalignant oral lesions would skew how immune cells respond to adipocyte-derived mediators to create an environment that may be more favorable for their progression toward cancer. While media conditioned by adipocytes stimulated normal spleen cell production of the T helper (Th) type-1 cytokines interleukin (IL)-2, interferon-γ (IFN-γ), IL-12 and granulocyte-monocyte colony-stimulating factor (GM CSF), media from premalignant lesion cells either blocked or had no added affect on the adipocyte-stimulated Th1 cytokine production. In contrast, media conditioned by premalignant lesion cells exacerbated adipocyte-stimulated spleen cell production of the Th2 cytokines IL-10 and IL-13, although it did not further enhance the adipocyte-stimulated spleen cell production of IL-4 and TGF-β. The premalignant lesion environment also heightened the adipocyte-stimulated spleen cell production of the inflammatory mediators IL 1α, IL-1β, IL-6 and IL-9, although it did not further increase the adipocyte-stimulated production of tumor necrosis factor-α (TNF-α). IL 17 production was unaffected by the adipocyte-derived mediators, but was synergistically triggered by adding media from premalignant lesion cells. These stimulatory effects on spleen cell production of Th2 and inflammatory mediators were not induced in the absence of media conditioned by adipocytes. In contrast, media conditioned by adipocytes did not stimulate production of predominantly monocyte-derived chemokine C-X-C motif ligand (CXCL)9, chemokine C-C motif ligand (CCL)3 or CCL4, although it stimulated production of CCL2 and the predominantly T cell-derived chemokine CCL5, which was the only chemokine whose production was further increased by media from premalignant lesions

  4. CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp.

    Science.gov (United States)

    Silva, Kathlenn Liezbeth Oliveira; Melo, Larissa Martins; Perosso, Juliana; Oliveira, Bruna Brito; Santos, Paulo Sérgio Patto Dos; Eugênio, Flávia de Rezende; Lima, Valéria Marçal Felix de

    2013-11-08

    Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Desoxyribonucleic acid (DNA) synthesis in vitro by thymus and spleen cells of the rat after hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Tempel, K.; Spath, A.

    1988-03-01

    The inhibition of the semiconservative and restorative DNA synthesis caused by hyperthermia (30 to 60 min, 43/sup 0/C) was significantly higher in spleen cells than in thymus cells. The DNA repair synthesis of thymus cells measured at 37/sup 0/C was increased by about two times the initial value after a pre-incubation of 30 to 90 min and 30 to 60 min, respectively, with 37 and 43/sup 0/C, respectively. Under the same conditions, the /sup 3/H-thymidine incorporation into the DNA of spleen cells diminished proportionally to the pre-incubation time after a pre-incubation of 30 and 45 min, respectively, with 43 and 37/sup 0/C, respectively. When hyperthermia and inhibitors of DNA synthesis or DNA repair (hydroxyurea, 1-..beta..-D-arabinofuranosylcytosine, 3', 5'-didesoxythymidine, and 3-aminobenzamide) were combined, overadditive effects - without cellspecific particularities - were seen only in the case of 3-aminobenzamide. Only in thymus cells, the inhibitor of DNA topoisomerase II novobiocin caused an overadditive reinforcement of the inhibition induced by hyperthermia of the semiconservative DNA synthesis. The stimulation of DNA repair synthesis in thymus cells caused by novobiocin with the aid of DNA polymerase ..beta.. could be compensated by hyperthermia. The sedimentation of thymus and spleen cell nucleoids was increased after hyperthermia. The results suggest a special importance of DNA topology and of the DNA polymerase ..beta.. activity for the cellular effect of hyperthermia.

  6. Histological Lesions, Cell Cycle Arrest, Apoptosis and T Cell Subsets Changes of Spleen in Chicken Fed Aflatoxin-contaminated Corn

    Directory of Open Access Journals (Sweden)

    Xi Peng

    2014-08-01

    Full Text Available The purpose of this study was to evaluate the effects of corn naturally contaminated with aflatoxin B1 and aflatoxin B2 on pathological lesions, apoptosis, cell cycle phases and T lymphocyte subsets of spleen, and to provide an experimental basis for understanding the mechanism of aflatoxin-induced immunosuppression. A total of 900 COBB500 male broilers were randomly allocated into five groups with six replicates per group and 30 birds per replicate. The experiment lasted for 6 weeks and the five dietary treatments consisted of control, 25% contaminated corn, 50% contaminated corn, 75% contaminated corn and 100% contaminated corn groups. The histopathological spleen lesions from the contaminated corn groups was characterized as congestion of red pulp, increased necrotic cells and vacuoles in the splenic corpuscle and periarterial lymphatic sheath. The contaminated corn intake significantly increased relative weight of spleen, percentages of apoptotic splenocytes, induced cell cycle arrest of splenocytes, increased the percentages of CD3+CD8+ T cells and decreased the ratios of CD3+CD4+ to CD3+CD8+. The results suggest that AFB-induced immunosuppression maybe closely related to the lesions of spleen.

  7. GM-CSF augments the immunosuppressive capacity of neonatal spleen cells in vitro

    International Nuclear Information System (INIS)

    Morrissey, P.J.; Ireland, R.

    1991-01-01

    Addition of exogenous granulocyte-macrophage colony stimulating factor (GM-CSF) to cultures of adult murine spleen cells with sheep red blood cells (SRBC) results in an augmented plaque forming cell (PFC) response. The influence of GM-CSF on the ability of neonatal spleen cells to suppress the anti-SRBC plaque forming response of adult spleen cells was tested by adding GM-CSF to cultures of neonatal and adult spleen cells. The suppressive capacity of the neonatal spleen cells was augmented by exogenous GM-CSF. The augmented suppression of the neonatal spleen cells was dependent on a G-10 adherent population since the addition of GM-CSF to cultures containing G-10 passed neonatal spleen cells resulted in an augmented PFC response and not suppression. Neonatal splenic glass adherent cells were also capable of suppressing the response. Neonatal spleen cells or purified neonatal glass adherent spleen cells cultured in the presence of GM-CSF had markedly increased levels of PGE2 in the culture supernatant. Neonatal spleen cells cultured with GM-CSF had increased numbers of morphologically identifiable macrophages after 48 hr of culture. Both irradiation and G-10 passage of the neonatal spleen diminished the numbers of macrophages formed in response to GM-CSF, and both of these manipulations resulted in reversal of suppression in response to GM-CSF. Thus, the augmented suppressive capacity of neonatal spleen cells in response to GM-CSF is probably mediated by its ability to drive monocyte to macrophage differentiation as well as increase the suppressive capacity of the existing neonatal splenic macrophages by increasing their production of PGE2

  8. Transplantation of homologous bone marrow cells to lethally irradiated mice: changes in the spleen

    Energy Technology Data Exchange (ETDEWEB)

    Viktora, L; Hach, P; Zoubkova, M

    1975-01-01

    Bone marrow cell suspensions were administered intravenously to lethally irradiated mice. The number of colonies in the spleen and the regeneration of hematopoietic tissue in the spleen were studied on the 9th day after irradiation and transplantation. From a comparison of the histological picture and weight of the spleens, the authors conclude that the degree of regeneration of hematopoiesis in the spleen after irradiation and transplantation is reflected in the weight of the spleen as well as in the number of hematopoietic colonies.

  9. Active suppression of in vitro reactivity of spleen cells after BCG treatment

    International Nuclear Information System (INIS)

    Orbach-Arbouys, S.; Poupon, M.F.

    1978-01-01

    It was found that spleen cells from mice injected i.v. with large doses of BCG responded to PHA stimulation less intensely than did normal spleen cells. It was shown that nylon wool column purified BCG treated T cells also had a low PHA reactivity. Unfractionated spleen cells, adherent cells or T-enriched populations from BCG treated mice, when added to normal T cells lowered their PHA reactivity. When the same BCG treated cell populations were added to tumor cells in vitro, they inhibited their growth. (author)

  10. Protective Effects of Polysaccharides from Soybean Meal Against X-ray Radiation Induced Damage in Mouse Spleen Lymphocytes

    Directory of Open Access Journals (Sweden)

    Xin Yang

    2011-11-01

    Full Text Available The aim of this study was to investigate radioprotective effect of the polysaccharides from soybean meal (SMP against X-ray radiation-induced damage in mouse spleen lymphocytes. MTT and comet assay were performed to evaluate SMP’s ability to prevent cell death and DNA damage induced by radiation. The results show that, X-ray radiation (30 KV, 10 mA, 8 min (4 Gy can significantly increase cell death and DNA fragmentation of mouse spleen lymphocytes. Pretreatment with SMP for 2 h before radiation could increase cell viability, moreover, the SMP can reduce X-ray radiation-induced DNA damage. The percentage of tail DNA and the tail moment of the SMP groups were significantly lower than those of the radiation alone group (p < 0.05. These results suggest SMP may be a good candidate as a radioprotective agent.

  11. The effect of lysate of spleen cells after low dose radiation (LDR) on NK activity

    International Nuclear Information System (INIS)

    Lu Duicai; Su Liaoyuan

    2003-01-01

    To find effect of lysate of spleen cells after LDR on NK activity of CD 57 cells or non-CD 57 cells, lysate of spleen cells after LDR were extracted. McAb (anti CD 57 cells) was used to separate CD 57 cells from human peripheral blood by Panning direct method. The CD 57 cells and non-CD 57 cells were used as effective cells. K 562 cells labelled by 3 H-TdR were used as target cells. The ratio of effect cells to target cells was 10:1. NK activity of CD 57 cells or non-CD 5 -7 cells with the lysate of spleen cells after LDR was reflected by the efficiency of anti tumor cells. The 3 H-TdR incorporation in K 562 cells cultured with non-CD 57 cells was significantly lower than that with CD 57 cells. After use of the lysate of spleen cells after LDR, NK activities of CD 57 cells and non-CD 57 cells were 1.24 and 1.58 respectively. They were both increased obviously compared with control groups. The effect of anti K 562 cells of non-CD 57 cells is even greater than that of CD 57 cells. The lysate of spleen cells after LDR can enhance the effect of both non-CD 57 cells and CD 57 cells

  12. Increased numbers of spleen colony forming units in B cell deficient CBA/N mice

    International Nuclear Information System (INIS)

    Wiktor-Jedrzejczak, W.; Krupienicz, A.; Scher, I.

    1986-01-01

    The formation of exogenous and endogenous spleen colonies was studied in immune-defective mice expressing the CBA/N X-linked xid gene. Bone marrow and spleen cells of immune deficient mice formed increased numbers of eight-day exogenous spleen colonies when transferred to either normal or B cell deficient lethally irradiated recipients. Moreover, defective mice showed increased formation of five-day endogenous spleen colonies (derived from transient endogenous colony forming units; T-CFU) and of ten-day endogenous spleen colonies (derived from CFU-S). Among the possible mechanisms responsible for the observed effects, the most probable appears the one in which decreased numbers of B cell precursors stimulate stem cell pools through a feedback mechanism. (orig.) [de

  13. The spleen can influence the metastasis of AH130 hepatoma cells in rats.

    Science.gov (United States)

    Toyonaga, M; Hiraoka, T; Tanaka, H; Miyauchi, Y

    1993-06-01

    The effect of pathophysiological conditions due to disturbance of the spleen is still unclear. We studied the effects of splenectomy in normal and methylcellulose-induced hypersplenic rats on the development of pulmonary metastases created by intravenous injection of ascites containing AH130 hepatoma cells from male Hos-Donryu rats. Growth of metastatic lesions in the lung was not affected by splenectomy in normal rats, but was increased by splenectomy in hypersplenic rats. Overall, there were fewer pulmonary metastases in rats with hypersplenism, but after splenectomy rats with hypersplenism had a significantly greater number of metastases than did normal rats. The metastases rate correlated somewhat with changes in the blood coagulation and T lymphocyte profile. There is a relationship between the spleen and formation of metastases in cancer. Formation of metastases in the lung was affected most by splenectomy in hypersplenism. To elucidate the mechanism by which metastases are formed in the lung under these pathologic conditions, further studies on the exact role of the spleen are required.

  14. Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure.

    Science.gov (United States)

    Kim, Soochan; Han, Sinsuk; Lee, Ye Eun; Jung, Woong-Jae; Lee, Hyung Soo; Kim, Yong-Sun; Choi, Eun-Kyoung; Kim, Mi-Yeon

    2016-01-01

    The cellular prion protein is expressed in almost all tissues, including the central nervous system and lymphoid tissues. To investigate the effects of the prion protein in lymphoid cells and spleen structure formation, we used prion protein-deficient (Prnp(0/0)) Zürich I mice generated by inactivation of the Prnp gene. Prnp(0/0) mice had decreased lymphocytes, in particular, CD4 T cells and lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired expression of CCL19 and CCL21 in the spleen rather than altered chemokine receptor CCR7 expression. Importantly, some of the white pulp regions in spleens from Prnp(0/0) mice displayed impaired T zone structure as a result of decreased LTi cell numbers and altered expression of the lymphoid tissue-organizing genes lymphotoxin-α and CXCR5, although expression of the lymphatic marker podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3(-)CD4(+)IL-7Rα(+) LTi cells were rarely detected in impaired white pulp in spleens of these mice. These data suggest that the prion protein is required to form the splenic white pulp structure and for development of normal levels of CD4 T and LTi cells. Copyright © 2015. Published by Elsevier GmbH.

  15. Computed tomography of the spleen and liver in sickle cell disease

    International Nuclear Information System (INIS)

    Magid, D.; Fishman, E.K.; Siegelman, S.S.

    1984-01-01

    The spleen was assessed in 10 patients with sickle cell disease studied with computed tomography (CT) for abdominal pain and/or unexplained fever. Patients with homozygous sickle cell anemia were found to have small, densely calcified spleens with occasional low-density infarcts. Five of six had hepatomegaly, and there was one case each of hepatic abscess, infarcts, and hemochromatosis. All patients with heterozygous sickle cell disease were found to have splenomegaly, with a variety of findings including acute hemorrhage, acute and chronic infarcts, rupture, and possible sequestration. It was concluded that CT is useful for evaluating the status of the spleen and liver in symptomatic patients with sickle cell disease

  16. Regeneration of hemopoietic precursor cells in spleen organ cultures from irradiated mice: influence of genotype of cells injected and of the spleen microenvironment

    International Nuclear Information System (INIS)

    von Melchner, H.; Lieschke, G.J.

    1981-01-01

    The regeneration of hemopoietic precursor cells (colony-forming cells, CFC) was monitored in spleen organ cultures from lethally irradiated mice injected with 10(7) normal syngeneic or allogeneic bone marrow cells. The important role of the microenvironment in supporting hemopoiesis was confirmed by the failure of mutant S1/S1d spleens to support CFC regeneration in organ cultures. However, the extent and quality of the CFC regeneration was clearly dependent on the genetic properties of the injected cells. Evidence for this was obtained from the regeneration patterns of various CFC types in organ cultured spleens derived from different mouse donor-recipient strain combinations (CBA/CBA, CBA/C57BL, CBA/BALB/c, C57BL/C57BL, C57BL/CBA, C57BL/BALB/c) that maintained the differences in the bone marrow frequency of various CFC types characteristic of the donor strain

  17. Phosphoprotein phosphatase of bovine spleen cell nuclei: physicochemical properties

    International Nuclear Information System (INIS)

    Rezyapkin, V.I.; Leonova, L.E.; Komkova, A.I.

    1986-01-01

    The physicochemical properties of phosphoprotein phosphatase (EC 1.3.1.16) from bovine spleen cell nuclei were studied. The enzyme possesses broad substrate specificity and catalyzes the dephosphorylation of phosphocasein, ATP, ADP, and p-nitrophenyl phosphate (pNPP). K/sub m/ for ATP, ADP, and pNPP are equal to 0.44, 0.43, and 1.25 mM, respectively. M/sub r/ of the enzyme, according to the data of gel filtraction of Sephadex G-75 and electrophoresis in polyacrylamide gel of various concentrations is ∼ 33,000. In electrophoresis in the presence of SDS, two protein bands with M/sub r/ 12,000 and 18,000 are detected. In the enzyme molecule, acid amino acid residues predominate; two free SH groups and two disulfide bridges are detected. Phosphoprotein phosphatase is a glycoprotein, containing ∼ 22% carbonhydrates. The protein possesses a supplementary absorption maximum at 560 nm. Ammonium molybdate is a competitive inhibitor with K/sub i/ 0.37 μM, while sodium fluoride is a noncompetitive inhibitor with K/sub i/ 1.3 mM. Incubation in the presence of 2 mM phenylmethylsulfonyl fluoride for 25 h leads to a loss of ∼ 46% of the enzymatic activity. Ammonium molybdate, sodium fluoride, and PMSF are reversible inhibitors. Modifications of the SH groups, NH 2 groups, and histidine leads to a decrease in the enzymatic activity. Incubation of phosphoprotein phosphatase with [γ- 32 P]ATP leads to the incorporation of 0.33 mole 33 P per mole of the enzyme. The mechanism of hydrolysis of the phosphodiester bond, catalyzed by the enzyme, is discussed

  18. Regeneration of hemopoietic precursor cells in spleen organ cultures from irradiated mice: influence of genotype of cells injected and of the spleen microenvironment

    International Nuclear Information System (INIS)

    von Melchner, H.; Lieschke, G.J.

    1981-01-01

    The regeneration of hemopoietic precursor cells was monitored in spleen organ cultures from lethally irradiated mice injected with 10(7) normal syngeneic or allogeneic bone marrow cells. The important role of the microenvironment in supporting hemopoiesis was confirmed by the failure of mutant Sl/Sld spleens to support CFC regeneration in organ cultures. However, the extent and quality of the CFC regeneration was clearly dependent on the genetic properties of the injected cells. Evidence for this was obtained from the regeneration patterns of various CFC types in organ cultured spleens derived from different mouse donor-recipient strain combinations that maintained the differences in the bone marrow frequency of various CFC types characteristic of the donor strain

  19. Selenium antagonizes cadmium-induced apoptosis in chicken spleen but not involving Nrf2-regulated antioxidant response.

    Science.gov (United States)

    Chen, Menghao; Li, Xiaojing; Fan, Ruifeng; Cao, Changyu; Yao, Haidong; Xu, Shiwen

    2017-11-01

    The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl 2 , 150mg/kg) and sodium selenite (Na 2 SeO 3 , 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days. The results showed that Cd exposure increased the level of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) and decreased the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (Gpx), total antioxidative capacity (T-AOC), catalase (CAT). Cd exposure increased obviously nuclear accumulation of Nrf2, and the expression of Nrf2 downstream heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO1), reduced the expression of Kelch-like ECH-associated protein (keap1), Gpx-1 and thioredoxin reductase-1 (TrxR1). In addition, Cd induced the increase of bak, caspase9, p53, Cyt c mRNA levels, increased bax/bcl-2 ratio, increased caspase3 mRNA and protein levels. Selenium treatment reduced the accumulation of Cd in the spleen, attenuates Cd-induced Nrf2 nuclear accumulation, enhanced antioxidant enzyme activities, ameliorated Cd-induced oxidative stress and apoptosis in the spleen. In summary, our results demonstrate that Se ameliorated spleen toxicity induced by cadmium by modulating the antioxidant system, independently of Nrf2-regulated antioxidant response pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Role of lycopene against spleen oxidative stress induced by sodium fluoride and gamma rays:Ultrastructural Changes

    International Nuclear Information System (INIS)

    Abd El Azeem, M.G.

    2011-01-01

    In connection with earlier studies, response of spleen ultrastructure effects of sodium fluoride (NaF) was examined. Sodium fluoride is a serious public health problem in many parts of the world, as in the case of many chronic degenerative diseases, increased production of reactive oxygen species has been considered to play an important role, even in the pathogenesis of chronic fluoride toxicity. Ionizing radiation (IR) is known to induce oxidative stress through generation of reactive oxygen species (ROS) resulting in imbalance of the pro-oxidant and antioxidant in the cells, which is suggested to culminate in cell death. The present study have been designed to evaluate the possible protective role of lycopene on spleen injure from the sodium fluoride (NaF) and gamma radiation in male mice. Ultrastructural studies were utilized for evaluation of these oxidative stress. Results showed that mice received (NaF) dose, lymphocyte revealed most appear with crystallized acicular structures and large specific 2 Gy granules they have dense internal crystalloid structure of variable shapes and densities. Interstitial haemorrhage, inflammatory area and, pyknotic nuclei with dense nuclear chromatin were observed .Their cytoplasm contained dilated endoplasmic reticulum, and active lysosomes as a result of the stress action of NaF. Whole body exposure of male mice to 2 Gy gamma radiation showing lymphocytes have pyknotic nuclei with dense nuclear chromatin, swollen mitochondria and active lysosomes, and fragmented of endoplasmic reticulum were also seen. The bundles of collagen fibrils among of the peri lymphocyte space accompanied with vacuolated cytoplasm area. Treatment of mice with lycopene (5 mg/kg, oral gavage) for 7 days, before NaF or IR, ameliorated the ultrastructural injury of the spleen induced by NaF and/or IR. Therefore, the present results revealed that lycopene has a protective effect against NaF and/or IR-induced spleen toxicity by antagonizing the free

  1. Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II

    Directory of Open Access Journals (Sweden)

    Ning-Ping Wang

    2017-05-01

    Full Text Available Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.

  2. Interleukin production by neonatal spleen cells during and as a result of antigen presentation: The effect of ultraviolet light

    International Nuclear Information System (INIS)

    Levin, D.; Gershon, H.

    1989-01-01

    Antigen presentation by neonatal murine spleen cells and the production of lymphokines and interleukins involved in the stimulation of a T-helper-2 (TH2) cell line (D10-G4.1) were studied as were the effects of ultra violet (UV)-irradiation on this system. Neonatal spleen cells are less capable than adult cells of performing the initial steps of the immune response required for antigen dependent activation of TH2 cells. These steps include soluble antigen processing and presentation and as a result reduced production of IL-4 and IL-1-Inducer Factor (IL-1-IF) by the T-helper cells and reduced production of IL-1 and IL-2 by the antigen presenting cell population. Spontaneous membrane IL-1 activity is low in the neonate, however, when exposed to IL-1-IF they can express adult levels. Ultraviolet (UV) irradiation of the antigen presenting population has a damaging effect on all the above mentioned processes. Antigen processing and presentation, induction of D10 IL-4 production and proliferation, and IL-2 production demonstrate two different age related patterns of UV-irradiation induced damage: a dose dependent inhibition when adult cells are irradiated and an inverse effect in which low doses of irradiation were more inhibitory than higher doses when neonatal cells are irradiated. However, the secretion and membrane expression of IL-1 by both age groups are directly and totally inhibited by the range of UV-irradiation doses used and cannot be reinduced with a supplement of a crude IL-1-IF. While the capacity to produced IL-1 is totally destroyed by UV-irradiation, the ability to produce IL-2 remains intact and remains responsive to an IL-2-Inducer activity during proper antigen presentation. The low responses of neonatal antigen presenting spleen cell populations and the damaging effect of UV on both neonatal and adult responses are not due to the induction of suppressor factors

  3. Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

    Directory of Open Access Journals (Sweden)

    William P Lafuse

    Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

  4. Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

    Science.gov (United States)

    Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

    2011-01-01

    It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

  5. Effects of cortisol on the primary response of mouse spleen cell cultures to heterologous erythrocytes

    International Nuclear Information System (INIS)

    Dracott, B.N.

    1974-01-01

    Cell viability and the production of direct PFC were studied in mouse spleen cell cultures after cortisol treatment in vivo or in vitro at various times relative to primary stimulation with SRBC in vitro. Cortisol treatment in vivo reduced spleen cell numbers by 88 percent after 48 hr, but cultures of the remaining cells produced as many PFC in vitro as did cultures of equal numbers of normal spleen cells. In normal spleen cell cultures incubated with cortisol for 4 hr prior to the addition of antigen, peak responses of PFC/culture and PFC/10 6 cells occurred 24 hr later than in controls and averaged, respectively, 27 and 141 percent of control values. Minimum viable cell numbers were observed in cortisol-treated cultures after 3 days; thereafter cell numbers gradually increased. These results were not significantly altered when cultures were treated simultaneously with cortisol and antigen. The response was not suppressed if the addition of antigen preceded that of cortisol by more than 4 hr. Suppression was also considerably reduced if fetal calf serum was used when preparing cells for culture

  6. Agaricus blazei Murill Polysaccharides Protect Against Cadmium-Induced Oxidative Stress and Inflammatory Damage in Chicken Spleens.

    Science.gov (United States)

    Xie, Wanqiu; Lv, Ai; Li, Ruyue; Tang, Zequn; Ma, Dexing; Huang, Xiaodan; Zhang, Ruili; Ge, Ming

    2018-07-01

    Agaricus blazei Murill polysaccharide (ABP) has exhibited antioxidant and immunoregulatory activity. The aim of this study was to investigate the effect of ABP on cadmium (Cd)-induced antioxidant functions and inflammatory damage in chicken spleens. In this study, groups of 7-day-old chickens were fed with normal saline (0.2 mL single/day), CdCl 2 (140 mg/kg/day), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP (140 mg/kg/day + 0.2 mL ABP). Spleens were separated on the 20th, 40th, and 60th day for each group. The Cd contents, expression of melanoma-associated differentiation gene 5 (MDA5) and its downstream signaling molecules (interferon promoter-stimulating factor 1 (IPS-1), transcription factors interferon regulatory factor 3 (IRF3), and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB)), the content of cytokines (interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and beta interferon (IFN-β)), protein levels of heat shock proteins (HSPs), levels of malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and histopathological changes of spleens were detected on the 20th, 40th, and 60th day. The results showed that ABP significantly reduced the accumulation of Cd in the chicken spleens and reduced the expression of MDA5, IPS-1, IRF-3, and NF-κB; their downstream inflammatory cytokines, IL-1β, IL-6, TNF-α, and IFN-β; and the protein levels of HSPs (HSP60, HSP70, and HSP90) in spleens. The activities of antioxidant enzymes (SOD and GSH-Px) significantly increased, and the level of MDA decreased in the ABP + Cd group. The results indicate that ABP has a protective effect on Cd-induced damage in chicken spleens.

  7. Migration inhibition of immune mouse spleen cells by serum from x-irradiated tumor-bearing mice

    International Nuclear Information System (INIS)

    Moroson, H.

    1978-01-01

    Tumor-specific antigens of the chemically induced MC 429 mouse fibrosarcoma were detected in a 3 M KCl extract of tumor by the inhibition of migration of specifically immune spleen cells. Using this assay with serum from tumor-bearing mice no tumor antigen was detected in serum of mice bearing small tumors, unless the tumor was exposed to local x irradiation (3000 R) 1 day prior to collection of serum. It was concluded that local x irradiation of tumor caused increased concentration of tumor antigen in the serum. When the tumor was allowed to grow extremely large, with necrosis, then host serum did cause migration inhibition of both nonimmune and immune spleen cells. This migration-inhibition effect was not associated with tumor antigen, but with a nonspecific serum factor

  8. Intermittent feeding as a factor enhancing hemopoietic stem cell proliferation and spleen colony formation in irradiated mice

    International Nuclear Information System (INIS)

    Kozubik, A.; Pospisil, M.

    1985-01-01

    The influence of metabolic stimulation induced by a 3 weeks' adaption of the animals to intermittent food intake on hemopoietic stem cells was investigated in mice. The methods used included transplantation of bone marrow to lethally irradiated recipients, assay of CFUs number, seeding efficiency, and incorporation of 125 iodode oxyuridine into the DNA of spleen cells. A stimulatory effect of the metabolically influenced hemopoietic environment on the proliferative activity in stem cell compartments and on the recovery of hemopoietic organs was demonstrated. These stimulatory effects were most marked when the bone marrow of metabolically influenced donors was transplanted to similarly influenced recipients. (orig.)

  9. Bulk enrichment of transplantable hemopoietic stem cell subsets from lipopolysaccharide-stimulated murine spleen

    International Nuclear Information System (INIS)

    Ploemacher, R.E.; Brons, R.H.; Leenen, P.J.

    1987-01-01

    Counterflow centrifugal elutriation (CCE) in combination with density flotation centrifugation and fluorescence-activated cell sorting on wheat-germ agglutinin-FITC(WGA)-binding cells within the light-scatter ''blast window'' were used consecutively to enrich pluripotent hemopoietic stem cells (HSC) in bulk from lipopolysaccharide-stimulated mouse spleen. The medium-to-strong WGA + ve fraction contained 3.10(6) cells isolated from 3-4 X 10(9) spleen cells, with an average of 126% day-12 CFU-S and 65% day-8 CFU-S as calculated on the basis of their seeding fraction, suggesting that virtually all cells represented in vivo macroscopic colony formers. In view of the large differences reported elsewhere between stem cell subsets differing in reconstitutive capacity and secondary stem cell generation ability, we also studied various isolated cell fractions with respect to spleen colony formation, radioprotective ability, and spleen- and marrow- repopulating ability. Day-8 and day-12 CFU-S copurified when isolated by CCE. Cells from a fraction with high affinity for WGA were most highly enriched for their radioprotective ability (RPA) and their ability to repopulate the cellularity of the spleen and femur of irradiated recipients. This fraction contained virtually pure day-12 CFU-S. However, the ability to generate secondary day-12 CFU-S and CFU-GM in irradiated organs was enriched most in the medium WGA + ve cell fraction. MRA and SRA, according to the latter criteria, could therefore be partly separated from day-12 CFU-S and RPA on the basis of affinity for WGA. The data strongly suggest that at least part of all day-12 CFU-S have a high potential to proliferate and differentiate into mature progeny, but a relatively low self-renewal ability, and may therefore not be representative of the genuine stem cell

  10. The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Naoaki Sakata

    2018-05-01

    Full Text Available This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

  11. The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells.

    Science.gov (United States)

    Sakata, Naoaki; Yoshimatsu, Gumpei; Kodama, Shohta

    2018-05-07

    This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

  12. Reactive Hypertrophy of an Accessory Spleen Mimicking Tumour Recurrence of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Christin Tjaden

    2011-01-01

    Full Text Available De novo occurrence of an accessory spleen after splenectomy is worth noting for two reasons. First, it is known that splenectomy can cause reactive hypertrophy of initially inactive and macroscopically invisible splenic tissue. Second, it can mimic tumour recurrence in situations in which splenectomy has been performed for oncological reasons. This might cause difficulties in differential diagnosis and the clinical decision for reoperation. We report the case of a patient with suspected recurrence of renal cell carcinoma after total pancreatectomy and splenectomy for metastatic renal cell carcinoma, which finally revealed an accessory spleen as the morphological correlate of the newly diagnosed mass in the left retroperitoneum.

  13. Expression of Immunoglobulin Receptors with Distinctive Features Indicating Antigen Selection by Marginal Zone B Cells from Human Spleen

    Science.gov (United States)

    Colombo, Monica; Cutrona, Giovanna; Reverberi, Daniele; Bruno, Silvia; Ghiotto, Fabio; Tenca, Claudya; Stamatopoulos, Kostas; Hadzidimitriou, Anastasia; Ceccarelli, Jenny; Salvi, Sandra; Boccardo, Simona; Calevo, Maria Grazia; De Santanna, Amleto; Truini, Mauro; Fais, Franco; Ferrarini, Manlio

    2013-01-01

    Marginal zone (MZ) B cells, identified as surface (s)IgMhighsIgDlowCD23low/−CD21+CD38− B cells, were purified from human spleens, and the features of their V(D)J gene rearrangements were investigated and compared with those of germinal center (GC), follicular mantle (FM) and switched memory (SM) B cells. Most MZ B cells were CD27+ and exhibited somatic hypermutations (SHM), although to a lower extent than SM B cells. Moreover, among MZ B-cell rearrangements, recurrent sequences were observed, some of which displayed intraclonal diversification. The same diversifying sequences were detected in very low numbers in GC and FM B cells and only when a highly sensitive, gene-specific polymerase chain reaction was used. This result indicates that MZ B cells could expand and diversify in situ and also suggested the presence of a number of activation-induced cytidine deaminase (AID)-expressing B cells in the MZ. The notion of antigen-driven expansion/selection in situ is further supported by the VH CDR3 features of MZ B cells with highly conserved amino acids at specific positions and by the finding of shared (“stereotyped”) sequences in two different spleens. Collectively, the data are consistent with the notion that MZ B cells are a special subset selected by in situ antigenic stimuli. PMID:23877718

  14. Perfluorononanoic acid-induced apoptosis in rat spleen involves oxidative stress and the activation of caspase-independent death pathway

    International Nuclear Information System (INIS)

    Fang, Xuemei; Feng, Yixing; Wang, Jianshe; Dai, Jiayin

    2010-01-01

    Perfluoroalkyl acid (PFAA)-induced apoptosis has been reported in many cell types. However, minimal information on its mode of action is available. This study explored the possible involvement of apoptotic signaling pathways in a nine-carbon-chain length PFAA-perfluorononanoic acid (PFNA)-induced splenocyte apoptosis. After a 14-day exposure to PFNA, rat spleens showed dose-dependent levels of apoptosis. The production of pro-inflammatory and anti-inflammatory cytokines was significantly increased and decreased, respectively. However, protein levels of tumor necrosis factor receptor 1 (TNFR1), fas-associated protein with death domain (FADD), caspase 8 and caspase 3, which are involved in inflammation-related and caspase-dependent apoptosis, were discordant. Peroxisome proliferator-activated receptors alpha (PPARα) and PPARγ genes expression was up-regulated in rats treated with 3 or 5 mg/kg/day of PFNA, and the level of hydrogen peroxide (H 2 O 2 ) increased concurrently in rats treated with the highest dose. Moreover, superoxide dismutase (SOD) activity and Bcl-2 protein levels were dramatically decreased in spleens after treatment with 3 and 5 mg/kg/day of PFNA. However, protein levels of Bax were unchanged. Apoptosis-inducing factor (AIF), an initiator of caspase-independent apoptosis, was significantly increased in all PFNA-dosed rats. Thus, oxidative stress and the activation of a caspase-independent apoptotic signaling pathway contributed to PFNA-induced apoptosis in rat splenocytes.

  15. Change of the NADPH depending superoxide producing and ferri hemoglobin reducing activities of cytochrome b558 from spleen cells and erythrocytes membranes induced by the radiation of different character

    International Nuclear Information System (INIS)

    Melkonyan, L.G.; Simonyan, R.M.; Simonyan, M.A.; Sekoyan, E.S.

    2009-01-01

    After the X radiation, UVA radiation and ultrasound radiation of new isoforms of cytochrome cyt b 5 58 from rats erythrocyte membranes - EM (cyt b 5 58III) and from spleen cell membranes (SCM) in vitro, as well as after the radiation of EM ex vivo, the suppression of both NADPH depending O 2 - producing and ferrihemoglobin (ferriHb)-reducing activities of cyt b 5 58 from EM and SCM in homogeneous (in solution) and heterogeneous phases (in EM and SCM) at various scopes takes place. These changes are associated with the destabilization of EM and SCM, conditioned by the change of the aggregation degree of these hemoproteins in EM and SCM, hemoproteins as a result of the influence of the hydrogen peroxide formed during radiolysis and photolysis of the water medium. After He-Ne laser radiation of the cyt b 5 58 from EM and SCM in vitro an increase of the NADPH depending O 2 - producing and ferriHb-reducing activities of the cyt b 5 58 from EM and SCM in homogenous and heterogeneous phases (in membranes) takes place. It is supposed that the suppression (by X-, UVA- and US-radiation) and the stimulation (by He-Ne laser radiation) of the immune system activity and the oxygen homeostasis are associated with the corresponding decrease and increase of the NADPH depending O 2 - producing and ferriHb-reducings activity of the new isoforms of cyt b 5 58 from EM and SCM in homogeneous and heterogeneous phases

  16. A stimulator of proliferation of spleen colony-forming cells (CFU-S) in the bone marrow of irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Ivanovic, Z.; Milenkovic, P.; Stojanovic, N.; Lukic, M.; Kataranovski, M.

    1993-07-01

    The presence and activity of a spleen colony - forming cell (CFU-S) proliferation stimulator was investigated in rat bone marrow after irradiation. The dose dependent increase in cytosine arabinoside induced cell dealth of normal mouse bone marrow. The results demonstrate the existence of a CFU-S proliferation stimulator in rat bone marrow similar to that originally found as a macrophage product in regenarating mouse bone marrow. The CFU-S proliferation stimulator activity was not associated with the presence of interleukin - 1,2, or 6 like activities in the material tested.

  17. Increased cell proliferation in spleen and lymph nodes peripheral to contact allergen application site

    International Nuclear Information System (INIS)

    Chipinda, Itai; Anderson, Stacey E.; Butterworth, Leon F.; Beezhold, Donald; Siegel, Paul D.

    2009-01-01

    The local lymph node assay (LLNA) is widely used to identify chemicals that are contact sensitizers. The assay involves dosing mice with the chemical on both ears and pooling the superficial parotid lymph nodes for assessment of lymphocyte proliferation as a marker of sensitization. The present study explored potential reduction in animal usage by dosing one ear with the allergen and the other with vehicle-only. The respective draining lymph nodes were processed separately for tritiated thymidine ( 3 H-TdR) incorporation. Cell proliferation in proper axillary and renal nodes, as well as in the spleen was also assessed. Cross-contamination of the chemicals from the dosed ears to other parts of the body via preening was prevented by dosing restrained animals and washing off the residual chemical with saline after 4 h. Dosing the left ear with 0.02% oxazolone (OX) on unrestrained animals resulted in marked cell proliferation in its draining lymph node (stimulation index, SI = 12.8) and in the lymph node draining the contra-lateral vehicle-dosed ear (SI = 6), as well as the proper axillary lymph nodes (SI = 3.3). Increased 3 H-TdR incorporation was not observed in the renal lymph nodes (SI = 1.1). Similar stimulation of cells was observed in the lymph node draining the ear contra-lateral to the 30% hexylcinnamaldehyde (HCA)-dosed ear. Increased proliferative activity was observed in contra-lateral draining lymph nodes of restrained mice demonstrating that these results cannot be attributed to cross-contamination of adjacent skin. A significant increase in proliferation of splenocytes was also observed. It is concluded that dermal application of a contact allergen, as exemplified by OX and HCA, may induce cell proliferation in the neighboring lymph nodes and spleen indicative of hapten and/or haptenated proteins diffusing through the skin to peripheral nodes and the blood to produce systemic sensitization. It is also possible that lymphatic capillaries may communicate

  18. Distinct CCR2(+) Gr1(+) cells control growth of the Yersinia pestis ΔyopM mutant in liver and spleen during systemic plague.

    Science.gov (United States)

    Ye, Zhan; Uittenbogaard, Annette M; Cohen, Donald A; Kaplan, Alan M; Ambati, Jayakrishna; Straley, Susan C

    2011-02-01

    We are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein YopM of the plague bacterium Yersinia pestis. In this study, we pursued previous findings that Gr1(+) cells are required to selectively limit growth of ΔyopM Y. pestis and that CD11b(+) cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parent Y. pestis. When PMNs were ablated from mice, ΔyopM Y. pestis grew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to ΔyopM Y. pestis in both organs. In spleen, the Gr1(+) cells differentially recruited by parent and ΔyopM Y. pestis infections were CCR2(+) Gr1(+) CD11b(+) CD11c(Lo-Int) MAC3(+) iNOS(+) (inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the ΔyopM mutant was relieved by the parent Y. pestis strain in a coinfection assay in which the parent strain could affect the fate of the mutant in trans. In a mouse model of bubonic plague, CCR2 also was shown to be required for ΔyopM Y. pestis to show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.

  19. Amplification of the spleen macrophage population in malaria: possible role of a factor chemotactic for blood mononuclear cells

    International Nuclear Information System (INIS)

    Wyler, D.J.; Gallin, J.I.

    1976-01-01

    The mechanism of amplification of the splenic macrophages' population was investigated using mice infected with malaria as a model of an obligate intravascular infection. It was observed that these macrophages derived from blood monocytes rather than by local proliferation in the spleen. A factor, chemotactic for blood mononuclear cells, was present in spleen cells shortly after infection and preceded detectable increases in spleen macrophage number by 48 hours. This factor, in concert with spleen derived macrophage migration inhibition factor, may be important in the amplification of splenic macrophage population in intravascular infections

  20. Heterogeneity within the spleen colony-forming cell population in rat bone marrow

    International Nuclear Information System (INIS)

    Martens, A.C.; van Bekkum, D.W.; Hagenbeek, A.

    1986-01-01

    The pluripotent hemopoietic stem cell (HSC) of the rat can be enumerated in a spleen colony assay (SCA) in rats as well as mice. After injection of rat bone marrow into lethally irradiated mice, macroscopically visible spleen colonies (CFU-S) are found from day 6 through 14, but the number varies on consecutive days. In normal bone marrow a constant ratio of day-8 to day-12 colony numbers is observed. However, this ratio is changed after in vivo treatment of rats with cyclophosphamide, as well as after in vitro treatment of rat bone marrow with cyclophosphamide derivatives. This indicates that the CFU-S that form colonies on day 8 react differently to this treatment than the CFU-S that form colonies on day 12, and suggests heterogeneity among the CFU-S population. Posttreatment regrowth of day-8 and day-12 CFU-S is characterized by differences in population-doubling times (Td = 0.85 days vs 1.65 days). Another argument in support of the postulate of heterogeneity within the rat CFU-S population is derived from the fact that (in contrast to normal rat spleen) the spleen of leukemic rats contains high numbers of CFU-S that show a ratio of day-8 to day-12 CFU-S of 4.5, which is different than that observed for a CFU-S population in normal bone marrow (a ratio of 2.4). It is concluded that, in rat hemopoiesis, two populations of spleen colony-forming cells can be distinguished using the rat-to-mouse SCA. This indicates that mouse and rat hemopoiesis are comparable in this respect and that heterogeneity in the stem cell compartment is a general phenomenon

  1. Bulk protein biosynthesis of the spleen and some splenic cell populations after induction of splenomegaly by application of Bordetella pertussis

    International Nuclear Information System (INIS)

    Krammenschneider, D.

    1980-01-01

    Autoradiographic studies and liquid scintillation counting were carried out in female NMRI mice just reaching maturity. All animals had received a single injection, either of bovine serum albumin (BSA) or of pertussis organism (PO) or BSA + PO. The animals were sacrificed 4 d and 10 d after this pretreatment. 2 h before decapitation, a single dose of 3 H-l phenyl alamine was applied intraperitoneally. The following results were obtained: The splenic index (splenic weight in mg/mouse weight in g) increased as a result of splenomegaly caused by PO. Morphometric data suggested an enlarged cell and nuclear area with enhanced cellular amino acid turnover and migration of RNP-containing matter into the nucleus, especially in the megakaryocytes and in lymphocytoid blastic cells. Incorporation of 3 H-l-phenylalanine per unit of dry weight of the spleen is slowed down during the experiment while amiro acid incorporation by the total spleen increases with PO-induced splenomegaly. Incorporation of amino acid per unit of dry weight is constant in all experimental and control animals. The increased amino acid incorporation in lymphocytoid blastic cells is probably caused by the immunological situations during the experiment. An explanation of total cell increase and cell increase of megakaryocytic splenic cells is attempted. (orig./MG) [de

  2. CD4+FOXP3+ cells produce IL-10 in the spleens of dogs with visceral leishmaniasis.

    Science.gov (United States)

    Silva, Kathlenn Liezbeth Oliveira; de Andrade, Mariana M C; Melo, Larissa M; Perosso, Juliana; Vasconcelos, Rosemeri O; Munari, Danisio P; Lima, Valéria M F

    2014-05-28

    Visceral Leishmaniasis (VL) is caused by intracellular parasites of the genus Leishmania that affect humans and several animal species. Dogs are one of the main urban reservoirs of the parasite and play a central role in the transmission cycle to humans via sandflies. Studies concerning the immune response in dogs with VL have demonstrated that protective immunity is associated with cellular immune response, while disease progression is associated with humoral response and IL-10 and TGF-β production. The study aimed to evaluate IL-10 and TGF-β production by regulatory T (Treg) cells in the blood and spleen of dogs naturally infected by Leishmania spp. and correlate this with parasite load. Five healthy dogs and 29 dogs with proven infection were selected for the study group. Real-time PCR was used to quantify parasite load and confirm infection by Leishmania spp. Treg cells producing IL-10 and TGF-β were quantified using flow cytometry. An increase in IL-10 production by Treg cells was verified in the spleen of dogs naturally infected by Leishmania spp. Concurrently, a decrease in the total number of T cells in these dogs was verified compared with healthy dogs. No association was determined between parasite load and the percentage of spleen Treg cells producing IL-10 and TGF-β. These findings suggest that Treg cells are an important source of IL-10 in the spleen, participating in immune response modulation, while the reduced percentage of these cells in infected dogs could be attributed to persistent immune activation. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. CT and MR findings of langerhans cell histiocytois involving the spleen: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Pyun, Hae Wook; Kim, Mee Eun; Kim, Jang Ho [Fatima Hospital, Taegu (Korea, Republic of)

    2002-02-01

    Langerhans cell histiocytosis (LCH) is systemic disease resulting from the proliferation and dissemination of abnormal histiocytic cells of the Langerhans cell system. Common sites of involvement include the skin, bone, bone marrow, lung, lymph nodes and central nervous system, and the condition manifests in variety of ways. We present the CT and MR findings of a case of LCH involving the spleen, an organ invloved relatively rarely. Post-contrast CT revealed multiple hypodense nodules. T1-weighted MR images of the spleen depicted no definitive lesion, but T2-weighted images showed abnormal low signals scattered throughout this organ. In addition, post-contrast, fat-saturated T1-weighted MR images lesions showed multiple, low-signal-intensity lesions.

  4. Intravenous delivery of HIV-based lentiviral vectors preferentially transduces F4/80+ and Ly-6C+ cells in spleen, important target cells in autoimmune arthritis.

    Directory of Open Access Journals (Sweden)

    Ben T van den Brand

    Full Text Available Antigen presenting cells (APCs play an important role in arthritis and APC specific gene therapeutic targeting will enable intracellular modulation of cell activity. Viral mediated overexpression is a potent approach to achieve adequate transgene expression levels and lentivirus (LV is useful for sustained expression in target cells. Therefore, we studied the feasibility of lentiviral mediated targeting of APCs in experimental arthritis. Third generation VSV-G pseudotyped self-inactivating (SIN-LV were injected intravenously and spleen cells were analyzed with flow cytometry for green fluorescent protein (GFP transgene expression and cell surface markers. Collagen-induced arthritis (CIA was induced by immunization with bovine collagen type II in complete Freund's adjuvant. Effect on inflammation was monitored macroscopically and T-cell subsets in spleen were analyzed by flow cytometry. Synovium from arthritic knee joints were analyzed for proinflammatory cytokine expression. Lentiviruses injected via the tail vein preferentially infected the spleen and transduction peaks at day 10. A dose escalating study showed that 8% of all spleen cells were targeted and further analysis showed that predominantly Ly6C+ and F4/80+ cells in spleen were targeted by the LV. To study the feasibility of blocking TAK1-dependent pathways by this approach, a catalytically inactive mutant of TAK1 (TAK1-K63W was overexpressed during CIA. LV-TAK1-K63W significantly reduced incidence and arthritis severity macroscopically. Further histological analysis showed a significant decrease in bone erosion in LV-TAK1-K63W treated animals. Moreover, systemic Th17 levels were decreased by LV-TAK1-K63W treatment in addition to diminished IL-6 and KC production in inflamed synovium. In conclusion, systemically delivered LV efficiently targets monocytes and macrophages in spleen that are involved in autoimmune arthritis. Moreover, this study confirms efficacy of TAK1 targeting in

  5. Oral Exposure to Atrazine Induces Oxidative Stress and Calcium Homeostasis Disruption in Spleen of Mice

    Directory of Open Access Journals (Sweden)

    Shuying Gao

    2016-01-01

    Full Text Available The widely used herbicide atrazine (ATR can cause many adverse effects including immunotoxicity, but the underlying mechanisms are not fully understood. The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice. ATR at doses of 0, 100, 200, or 400 mg/kg body weight was administered to Balb/c mice daily for 21 days by oral gavage. The studies performed 24 hr after the final exposure showed that ATR could induce the generation of reactive oxygen species in the spleen of the mice, increase the level of advanced oxidation protein product (AOPP in the host serum, and cause the depletion of reduced glutathione in the serum, each in a dose-related manner. In addition, DNA damage was observed in isolated splenocytes as evidenced by increase in DNA comet tail formation. ATR exposure also caused increases in intracellular Ca2+ within splenocytes. Moreover, ATR treatment led to increased expression of genes for some antioxidant enzymes, such as HO-1 and Gpx1, as well as increased expression of NF-κB and Ref-1 proteins in the spleen. In conclusion, it appears that oxidative stress and disruptions in calcium homeostasis might play an important role in the induction of immunotoxicity in mice by ATR.

  6. Littoral cell angioma of the spleen: CT and MR imaging appearance

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, G.; Uder, M.; Altmeyer, K.; Gruber, M.; Kramann, B. [Univ. Hospital Saarland University, Homburg/Saar (Germany). Dept. of Diagnostic Radiology; Bonkhoff, H. [Department of Pathology, University Hospital, Saarland University, D-66421 Homburg/Saar (Germany)

    2000-09-01

    We report a case of littoral cell angioma (LCA) of the spleen, a recently described splenic pathology, which imaging characteristics and pathologic morphology have been discussed only by a few authors. The imaging findings in unenhanced and contrast-enhanced MRI and CT as well as histologic specimen are presented. Diagnosis was made after elective splenectomy. Differential diagnosis of splenic tumors as well as the imaging findings in this particular case are discussed. (orig.)

  7. The effect of iron-deficiency anemia on cytolytic activity of mice spleen and peritoneal cells against allogenic tumor cells

    International Nuclear Information System (INIS)

    Kuvibidila, S.R.; Baliga, B.S.; Suskind, R.M.

    1983-01-01

    The capacity of spleen and peritoneal cells from iron deficient mice, ad libitum fed control mice, and pair-fed mice to kill allogenic tumor cells (mastocytoma tumor P815) has been investigated. In the first study, mice were sensitized in vivo with 10(7) viable tumor cells 51 and 56 days after weaning. The capacity of splenic cells and peritoneal cells from sensitized and nonsensitized mice to kill tumor cells was evaluated 5 days after the second dose of tumor cells. At ratios of 2.5:1 to 100:1 of attacker to target cells, the percentage 51 Cr release after 4 h of incubation was significantly less in iron-deficient mice than control and/or pair-fed mice (p less than 0.05). Protein-energy undernutrition in pair-fed mice had no significant effect. In the second study, spleen cells and enriched T cell fractions were incubated in vitro for 5 days with uv irradiated Balb/C spleen cells in a 2:1 ratio. The cytotoxic capacity against the same allogenic tumor cells was again evaluated. The percentage chromium release at different attacker to target cells was less than 30% in the iron-deficient group compared to either control or pair-fed supporting the results of in vivo sensitized cells. The possible mode of impairment of the cytotoxic capacity is discussed

  8. Spleen scanning with 99Tcsup(m)-labelled red blood cells after splenectomy

    International Nuclear Information System (INIS)

    Spencer, G.R.; Bird, C.; Prothero, D.L.; Brown, T.R.; Mackenzie, F.A.F.; Phillips, M.J.

    1981-01-01

    In order to correlate the haematological changes which occur after splenectomy, with the presence or absence of residual splenic tissue, spleen scans using 99 Tcsup(m)-labelled red blood cells were performed in 36 patients who had had a splenectomy. Positive spleen scans were found in 44 per cent (8 out of 18) of patients who had undergone splenectomy for trauma and in 17 per cent (3 out of 18) of patients who had undergone elective splenectomy. No relationship was found between the presence of Howell-Jolly bodies, platelet counts, the levels of IgG, IgM and IgA and the scan result. It is concluded that these findings are due to the presence of splenunculi, whose incidence is more common than the 12 per cent usually quoted. (author)

  9. Exogenous cytokines released by spleen and Peyer's patch cells removed from mice infected with Giardia muris.

    Science.gov (United States)

    Djamiatun, K; Faubert, G M

    1998-01-01

    The role that T and B lymphocytes play in the clearance of Giardia muris in the mouse model is well known, but the cytokines produced by CD4+ T cells in response to Giardia antigenic stimulation are unknown. In this study, we have determined how Giardia trophozoite antigenic crude extract and T cell mitogens can trigger the production of cytokines by Peyer's patch and spleen cells removed from infected animals. When Giardia trophozoite proteins were used to challenge the cells in vitro, IL-4, IL-5 and IFN-gamma were not detected in the culture supernatant. When the cells were challenged with Con-A, all three cytokines were released in vitro. However, the level of each cytokine released by the spleen or Peyer's patch cells varied with the latent, acute and elimination phases of the infection. The high levels of IL-4 and IL-5 released by Peyer's patch cells confirm the importance of IgA in the control of the infection. However, we propose that the relative success of G. muris in completing its life cycle in a primary infection might be due, in part, to the stimulation of a Th2-type response (IL-4, IL-5). A stronger Th1 response (IFN-gamma) may lead to a better control of the primary infection.

  10. HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis

    Science.gov (United States)

    Harrington, Willie; Bond, Vincent; Huang, Ming Bo; Powell, Michael; Lillard, James; Manne, Upender; Bumpers, Harvey

    2010-01-01

    CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1α, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis. PMID:20383296

  11. Ultrasound-guided cytology of spleen and liver: a prognostic tool in canine cutaneous mast cell tumor.

    Science.gov (United States)

    Stefanello, D; Valenti, P; Faverzani, S; Bronzo, V; Fiorbianco, V; Pinto da Cunha, N; Romussi, S; Cantatore, M; Caniatti, M

    2009-01-01

    In the clinical staging of cutaneous mast cell tumors (cMCT), the diagnosis of metastasis is controversial based on cytological examination of lymph nodes, spleen, liver, bone marrow, and blood. To define the prognostic role of ultrasound-guided cytology of spleen and liver in cMCT. The results of cytological evaluation were compared in relation with survival time. Fifty-two client-owned dogs with a diagnosis of cMCT. Selection of cases was based on cytological evaluation of liver and spleen to detect infiltration at distant sites. The Kaplan Meier method was used to compare survival in dogs with and without infiltration of spleen and liver (log-rank test P dogs with cMCT had mast cell infiltration of spleen, liver, or both and 4 of these dogs had involvement of the regional lymph nodes. The majority of dogs had 2 or more ultrasonographically abnormal findings simultaneously in spleen and liver. Nine dogs had grade II cMCT, and 1 had grade III cMCT. Dogs with positive evidence of mast cell infiltration to spleen, liver, or both had shorter survival times (34 versus 733 days) compared with dogs negative for mast cell infiltration at distant sites. Dogs with evidence of mast cell infiltration at distant sites have a shorter survival times than dogs without evidence of infiltration at distant sites. This study suggests that cytology of spleen and liver is indicated either for ultrasonographically normal or for ultrasonographically abnormal spleen and liver in dogs with cMCT.

  12. Ability of spleen cells from tumor bearing mice to transfer immunologic memory

    Energy Technology Data Exchange (ETDEWEB)

    Plavsic, B.; Jurin, M. (Zagreb Univ. (Yugoslavia)); Ugarkovic, B. (Institut Rudjer Boskovic, Zagreb (Yugoslavia))

    1983-01-01

    The ability of splenocytes from tumorous mice to transfer immunologic memory was tested. Three syngeneic experimental tumors from highly inbred strains were used; fibrosarcoma, lymphoma and Lewis lung carcinoma. Splenocytes from tumorous mice were collected after rejection of allogeneic skin which had been grafted at different stages of the tumor disease, and injected into lethally irradiated syngeneic recipients. These secondary hosts were grafted with the same allogeneic skin graft as their donors and the ability of cells transplanted from tumorous donors to transfer memory to allograft was tested. Tumorous mice seemed to have more memory cells (T lymphocytes) in their spleens than the controls.

  13. Changes of red blood cell aggregation parameters in a long-term follow-up of splenectomy, spleen-autotransplantation and partial or subtotal spleen resections in a canine model.

    Science.gov (United States)

    Miko, Iren; Nemeth, Norbert; Peto, Katalin; Furka, Andrea; Toth, Laszlo; Furka, Istvan

    2017-01-01

    Decrease or loss in splenic filtration function may influence the hemorheological state. To follow-up the long-term effects of splenectomy, spleen autotransplantation and spleen resections on red blood cell aggregation in a canine model. Beagle dogs were subjected to control (n = 6), splenectomy (SE, n = 4), spleen autotransplantation (AU, Furka's spleen-chip method, n = 8) or partial and subtotal spleen resection (n = 4/each) groups, and followed-up for 18 postoperative (p.o.) months. Erythrocyte aggregation was determined in parallel by light-transmittance aggregometry (Myrenne MA-1 aggregometer) and syllectometry (LoRRca). Erythrocyte aggregation decreased three months after splenectomy, with lower aggregation index and elongated aggregation time. It was more or less associated with relatively lower hematocrit and fibrinogen concentration. However, in autotransplantated animals a relatively higher fibrinogen did not increase the aggregation markedly. Spleen resection resulted in the most controversial red blood cell aggregation findings, and it seems, that the degree of the resection is an influencing factor. Splenectomy alters erythrocyte aggregation, spleen autotransplantation can be useful to preserve filtration function. However, the degree of restoration shows individual differences with a kind of 'functional periodicity'. Spleen resection controversially influences erythrocyte aggregation parameters. The subtotal resection is supposed to be worse than spleen autotransplantation.

  14. Killing of targets by effector CD8 T cells in the mouse spleen follows the law of mass action

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory

    2009-01-01

    In contrast with antibody-based vaccines, it has been difficult to measure the efficacy of T cell-based vaccines and to correlate the efficacy of CD8 T cell responses with protection again viral infections. In part, this difficulty is due to poor understanding of the in vivo efficacy of CD8 T cells produced by vaccination. Using a: recently developed experimental method of in vivo cytotoxicity we have investigated quantitative aspects of killing of peptide-pulsed targets by effector and memory CD8 T cells, specific to three epitopes of lymphocytic choriomeningitis virus (LCMV), in the mouse spleen. By analyzing data on killing of targets with varying number of epitope-specific effector and memory CD8 T cells, we find that killing of targets by effectors follows the law of mass-action, that is the death rate of peptide-pulsed targets is proportional to the frequency of CTLs in the spleen. In contrast, killing of targets by memory CD8 T cells does not follow the mass action law because the death rate of targets saturates at high frequencies of memory CD8 T cells. For both effector and memory cells, we also find little support for the killing term that includes the decrease of the death rate of targets with target cell density. Interestingly, our analysis suggests that at low CD8 T cell frequencies, memory CD8 T cells on the per capita basis are more efficient at killing peptide-pulsed targets than effectors, but at high frequencies, effectors are more efficient killers than memory T cells. Comparison of the estimated killing efficacy of effector T cells with the value that is predicted from theoretical physics and based on motility of T cells in lymphoid tissues, suggests that limiting step in the killing of peptide-pulsed targets is delivering the lethal hit and not finding the target. Our results thus form a basis for quantitative understanding of the process of killing of virus-infected cells by T cell responses in tissues and can be used to correlate the

  15. Quantitative assay for the number of leukemic spleen colony forming unit in radiation-induced murine myeloid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Nara, N [Tokyo Medical and Dental Univ. (Japan). School of Medicine; Bessho, M

    1981-11-01

    In mice with myelogenous leukemia, leukemic spleen colony forming units were assayed quantitatively. When 5 x 10/sup 3/ - 2 x 10/sup 4/ leukemic cells were transplanted to other mice of the same strain, a rectilinear relationship (p < 0.01) was found between the number of the cells transplanted and that of the colonies formed on the surface of the spleen. From these results, the authors considered that myelogenous leukemia in mice is an adequate model for acute myelogenous leukemia in human adults, and that the quantitative assay of the leukemic colony forming units can be used for sensitivity tests of antileukemic agents.

  16. Wandering spleen

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yong Tai; Lee, Sun Hwa; Lee, Dong Ho; Ko, Young Tae; Lim, Jae Hoon [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1987-12-15

    Wandering spleen is a rare entity, which is defined as the presence of the spleen in other than the left upper quadrant of the abdomen. The etiology of wandering spleen is unknown. Congenital factors such as incomplete fusion or laxity of the supporting structures of the spleen and acquired factors such as splenomegaly, trauma, abdominal laxity and hormonal effects of pregnancy may play a role. The clinical presentation is variable from asymptomatic to catastrophic if torsion of the splenic pedicle occurs. We present two cases of wandering spleen with a brief review of the literature.

  17. Wandering spleen

    International Nuclear Information System (INIS)

    Park, Yong Tai; Lee, Sun Hwa; Lee, Dong Ho; Ko, Young Tae; Lim, Jae Hoon

    1987-01-01

    Wandering spleen is a rare entity, which is defined as the presence of the spleen in other than the left upper quadrant of the abdomen. The etiology of wandering spleen is unknown. Congenital factors such as incomplete fusion or laxity of the supporting structures of the spleen and acquired factors such as splenomegaly, trauma, abdominal laxity and hormonal effects of pregnancy may play a role. The clinical presentation is variable from asymptomatic to catastrophic if torsion of the splenic pedicle occurs. We present two cases of wandering spleen with a brief review of the literature

  18. Sickle Cell Beta-Plus Thalassemia with Subcapsular Hematoma of the Spleen

    Directory of Open Access Journals (Sweden)

    Suyash Dahal

    2017-01-01

    Full Text Available While splenic complications like hypersplenism, sequestration crisis, and infarction are commonly reported in sickle cell variants like sickle cell beta-plus thalassemia, splenic rupture with hematoma is rare. We present a case of a 32-year-old young male who presented with dull left upper quadrant pain who was found to have multiple subcapsular splenic lacerations and hematoma on abdominal imaging. Hemoglobin electrophoresis confirmed sickle cell beta-plus thalassemia in the patient. There was no history of trauma, and rest of the workup for possible cause of spontaneous rupture of spleen was negative. With the patient refusing splenectomy, he was managed conservatively. Clinicians need to be aware of this rare complication of sickle cell variants.

  19. The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress.

    Science.gov (United States)

    Ren, Jiayi; Liu, Chunpeng; Zhao, Dan; Fu, Jing

    2018-05-15

    The aim of this study was to investigate the role of heat shock protein 70 (Hsp70) in oxidative stress and inflammatory damage in the spleen of quails which were induced by cold stress. One hundred ninety-two 15-day-old male quails were randomly divided into 12 groups and kept at 12 ± 1 °C to examine acute and chronic cold stress. We first detected the changes in activities of antioxidant enzymes in the spleen tissue under acute and chronic cold stress. The activities of glutathione peroxidase (GSH-Px) fluctuated in acute cold stress groups, while they were significantly decreased (p stress. The activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) content were decreased significantly (p stress groups. Malondialdehyde (MDA) content was significantly increased (p stress except the 0.5 h group of acute cold stress. Besides, histopathological analysis showed that quail's spleen tissue was inflammatory injured seriously in both the acute and chronic cold stress groups. Additionally, the inflammatory factors (cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), iNOS, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-a (TNF-α)) and Hsp70 mRNA levels were increased in both of the acute and chronic cold stress groups compared with the control groups. These results suggest that oxidative stress and inflammatory injury could be induced by cold stress in spleen tissues of quails. Furthermore, the increased expression of Hsp70 may play a role in protecting the spleen against oxidative stress and inflammatory damage caused by cold stress.

  20. Aniline-induced nitrosative stress in rat spleen: Proteomic identification of nitrated proteins

    International Nuclear Information System (INIS)

    Fan Xiuzhen; Wang Jianling; Soman, Kizhake V.; Ansari, G.A.S.; Khan, M. Firoze

    2011-01-01

    Aniline exposure is associated with toxicity to the spleen which is characterized by splenomegaly, hyperplasia, fibrosis, and a variety of sarcomas on chronic exposure in rats. However, mechanisms by which aniline elicits splenotoxic responses are not well understood. Earlier we have shown that aniline exposure leads to increased nitration of proteins in the spleen. However, nitrated proteins remain to be characterized. Therefore, in the current study using proteomic approaches, we focused on characterizing the nitrated proteins in the spleen of aniline-exposed rats. Aniline exposure led to increased tyrosine nitration of proteins, as determined by 2D Western blotting with anti-3-nitrotyrosine specific antibody, compared to the controls. The analyzed nitrated proteins were found in the molecular weight range of 27.7 to 123.6 kDa. A total of 37 nitrated proteins were identified in aniline-treated and control spleens. Among them, 25 were found only in aniline-treated rats, 11 were present in both aniline-treated and control rats, while one was found in controls only. The nitrated proteins identified mainly represent skeletal proteins, chaperones, ferric iron transporter, enzymes, nucleic acids binding protein, and signaling and protein synthesis pathways. Furthermore, aniline exposure led to significantly increased iNOS mRNA and protein expression in the spleen, suggesting its role in increased reactive nitrogen species formation and contribution to increased nitrated proteins. The identified nitrated proteins provide a global map to further investigate alterations in their structural and functional properties, which will lead to a better understanding of the role of protein nitration in aniline-mediated splenic toxicity. - Highlights: → Proteomic approaches are used to identify nitrated proteins in the spleen. → Twenty five nitrated proteins were found only in the spleen of aniline-treated rats. → Aniline exposure led to increased iNOS mRNA and protein

  1. Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort.

    Directory of Open Access Journals (Sweden)

    Paul U Cameron

    Full Text Available Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591. A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140 were tested for IgM memory B cells. We also determined a changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b the kinetics of changes in haematological markers associated with splenectomy(n = 45. Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001 reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB, occurred early (median 25 days and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

  2. Splenectomy Associated Changes in IgM Memory B Cells in an Adult Spleen Registry Cohort

    Science.gov (United States)

    Cameron, Paul U.; Jones, Penelope; Gorniak, Malgorzata; Dunster, Kate; Paul, Eldho; Lewin, Sharon; Woolley, Ian; Spelman, Denis

    2011-01-01

    Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (psplenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population. PMID:21829713

  3. CD4/CD8/Dendritic cell complexes in the spleen: CD8+ T cells can directly bind CD4+ T cells and modulate their response

    Science.gov (United States)

    Barinov, Aleksandr; Galgano, Alessia; Krenn, Gerald; Tanchot, Corinne; Vasseur, Florence

    2017-01-01

    CD4+ T cell help to CD8+ T cell responses requires that CD4+ and CD8+ T cells interact with the same antigen presenting dendritic cell (Ag+DC), but it remains controversial whether helper signals are delivered indirectly through a licensed DC and/or involve direct CD4+/CD8+ T cell contacts and/or the formation of ternary complexes. We here describe the first in vivo imaging of the intact spleen, aiming to evaluate the first interactions between antigen-specific CD4+, CD8+ T cells and Ag+DCs. We show that in contrast to CD4+ T cells which form transient contacts with Ag+DC, CD8+ T cells form immediate stable contacts and activate the Ag+DC, acquire fragments of the DC membranes by trogocytosis, leading to their acquisition of some of the DC properties. They express MHC class II, and become able to present the specific Marilyn peptide to naïve Marilyn CD4+ T cells, inducing their extensive division. In vivo, these CD8+ T cells form direct stable contacts with motile naïve CD4+ T cells, recruiting them to Ag+DC binding and to the formation of ternary complexes, where CD4+ and CD8+ T cells interact with the DC and with one another. The presence of CD8+ T cells during in vivo immune responses leads to the early activation and up-regulation of multiple functions by CD4+ T lymphocytes. Thus, while CD4+ T cell help is important to CD8+ T cell responses, CD8+ T cells can interact directly with naïve CD4+ T cells impacting their recruitment and differentiation. PMID:28686740

  4. Serum ferritin in patients with cancer: determination with antibodies to HeLa cell and spleen ferritin

    International Nuclear Information System (INIS)

    Jones, B.M.; Worwood, M.; Jacobs, A.

    1980-01-01

    Some malignant tissues and cell lines contain acidic isoferritins and it has been suggested that the assay of such isoferritins in serum may be of value in the diagnosis of malignancy. This paper describes a radioimmunoassay for acidic ferritin purified from HeLa cells. Examination of purified heart, kidney, liver and spleen ferritin showed that the assay was highly specific for acidic isoferritins. Ferritin concentrations have been measured with antibodies to HeLa cell and spleen ferritin in extracts of normal and tumour tissue. Although the tumours contained more HeLa type ferritin than the corresponding normal tissue the HeLa/spleen type ferritin ratio was low. HeLa-type ferritin concentrations have been compared with values obtained with anti-spleen ferritin in over 1000 sera from normal subjects and patients with cancer and leukaemia. HeLa-type ferritin was not detected (<2 μg/l) in most normal sera. Concentrations of up to 53 μg/l were found in sera from patients with malignant disease but the HeLa/spleen type ferritin ratio was always very low. There appears to be little application for antibodies to HeLa cell or heart ferritin in the diagnosis or monitoring of cancer. (Auth.)

  5. MORPHOMETRY OF SPLEEN

    Directory of Open Access Journals (Sweden)

    Radhika

    2016-03-01

    Full Text Available INTRODUCTION Spleen is organ of lymphatic system located on left side of abdominal cavity under diaphragm. It is a secondary lymphatic organ that plays an important role in cell mediated immunity. Foetal spleen is erythropoietic in nature. MATERIAL & METHODS Present study was done in 50 adult spleens and 50 foetal spleens. RESULTS Morphometric features like length, breadth, thickness & weight are measured. Length varied from 6.3 to 12.5 cm, breadth varied from 2.6 to 8.6 cm, thickness ranged from 2 cm to 4.6 cm, weight ranged from 65 g to 225 g. Average total length of spleen is 2.52 cm x 1.76 x 2 cm, weight 6.5 g. Shapes of spleens observed wedge shape spleen–48%, tetrahedral spleen–24%, triangular spleen-28%. Splenic notches on superior border & inferior border are observed. Incident of accessory spleen in 1% of cases. CONCLUSIONS Present knowledge of study may be helpful for surgeons in surgical procedures like splenectomy, resection of tumours and extirpation of cysts

  6. Ruptured Spleen

    Science.gov (United States)

    ... be caused by various underlying problems, such as mononucleosis and other infections, liver disease, and blood cancers. ... cause a ruptured spleen. For instance, people with mononucleosis — a viral infection that can cause an enlarged ...

  7. Wandering Spleen

    International Nuclear Information System (INIS)

    Al-Mashat, Faisal M.; Sibiany, Abdulrehman M.; Maimani, Abdulraouf A.; Alem, Fayad K.

    2004-01-01

    Cogenital malformations of the spleen are rare. We report 3 cases of wandering spleen presented as abominal or pelvi-abdominal mass. Two patients were suffering from chronic lower abdominal pain with thrombosed splenic pedicle and the third patient had an acute abdomen. All patients underwent splenectomies. Abdominal ultrasound, computerized tomography, Doppler's ultrasound, and radioisotpes studies were used to cpnfirm the diagnosis. The clinical, diagnostic and treatment modalities are discussed. (author)

  8. Study of the kinetics and morphology of immune reaction spleen cells by immunocytoadherence method. IV

    International Nuclear Information System (INIS)

    Blazek, J.

    1976-01-01

    The course of immunocytoadherence was followed in the mouse spleen during primary immune response to intraperitoneal administration of sheep erythrocytes at 24 hours, 72 hours and 6 days following whole-body irradiation with a dose of 450 R after antigen administration. The number of RFC becomes reduced immediately after irradiation. The reduction thereof always correlates with a relative increase of macrophages. Small and medium-sized lymphocytes rapidly disappear from the population of rosette-forming cells. If the irradiation had been carried out before the radiation-uninfluenced reaction reached its maximum, the large lymphocytes relatively increase in number. In other cases their immunocytoadherent activity also shows a steadily decreasing tendency. During the primary reaction, irradiation always increases the total relative plasma cell count as related to the other RFC. In such cases the proportion of mature forms is larger than of blastic forms. The values observed at the end of the studied postirradiation period in the course of the primary reaction are always characterized by a higher proportion of the plasma cell line after about 20 to 25 days. (author)

  9. The nature of tolerance in adult recipient mice made tolerant of alloantigens with supralethal irradiation followed by syngeneic bone marrow cell transplantation plus injection of F1 spleen cells

    International Nuclear Information System (INIS)

    Tomita, Y.; Himeno, K.; Mayumi, H.; Tokuda, N.; Nomoto, K.

    1989-01-01

    The length of time after syngeneic bone marrow reconstitution when tolerance to alloantigens can be induced in adult mice during T cell differentiation from bone marrow cells was studied by exposing those T cells to (recipient x donor)F1 spleen cells. Supralethally irradiated C3H/He Slc(C3H; H-2k) mice were reconstituted with 1 x 10(7) syngeneic T cell-depleted bone marrow cells and then injected intravenously with 5 x 10(7) (C3H x C57BL/6[B6])F1 (B6C3F1; H-2bxk) or (C3H x AKR/J[AKR])F1 (AKC3F1; H-2kxk) spleen cells at various intervals. In the fully allogeneic combination of B6C3F1----C3H, EL-4 tumor originating from B6 was accepted, and survival of grafted B6 skin was significantly prolonged in the tolerant C3H mice treated with irradiation on day -1 followed by injection of syngeneic bone marrow cells on day 0 plus B6C3F1 spleen cells on days 0, 5, or 10, in a tolerogen-specific manner. In the multiminor histocompatibility antigen-disparate combination of AKC3F1----C3H, AKR skin grafts were permanently accepted in the tolerant C3H mice treated with AKC3F1 spleen cells on days 0, 5, 10, or 15. Immunological parameters, including cytotoxic T lymphocyte activity and delayed foot-pad reaction (DFR), were almost completely suppressed in C3H mice made tolerant of B6 or AKR antigens. A chimeric assay using a direct immunofluorescence method revealed that the tolerant C3H mice given B6C3F1 spleen cells on day 0 were mixed-chimeric for at least 8 weeks after syngeneic bone marrow reconstitution, but not definitely chimeric thereafter. The C3H mice given AKC3F1 spleen cells on day 0 were chimeric even 43 weeks after syngeneic bone marrow reconstitution, but the C3H mice given AKC3F1 spleen cells on day 15 showed temporal chimerism that disappeared within 43 weeks. The untolerant mice were never detectably chimeric

  10. Spleen-dependent immune protection elicited by CpG adjuvanted reticulocyte-derived exosomes from malaria infection is associated with T cells population changes.

    Directory of Open Access Journals (Sweden)

    Lorena Martin-Jaular

    2016-11-01

    Full Text Available Reticulocyte-derived exosomes (rex are 30-100 nm membrane vesicles of endocytic origin released during the maturation of reticulocytes to erythrocytes upon fusion of multivesicular bodies with the plasma membrane. Combination of CpG-ODN with rex obtained from BALB/c mice infected with the reticulocyte-prone non-lethal P. yoelii 17X malaria strain (rexPy, had been shown to induce survival and long lasting protection. Here, we show that splenectomized mice are not protected upon rexPy+CpG inmunizations and that protection is restored upon passive transfer of splenocytes obtained from animals immunized with rexPy+CpG. Notably, rexPy immunization of mice induced PD1- memory T cell expansion with effector phenotype. Proteomics analysis of rexPy confirmed their reticulocyte origin and demonstrated the presence of parasite antigens. Our studies thus prove, for what we believe is the first time, that rex from reticulocyte-prone malarial infections are able to induce splenic long-lasting memory responses. To try extrapolating these data to human infections, in vitro experiments with spleen cells of human transplantation donors were performed. Plasma-derived exosomes from vivax malaria patients (exPv were actively uptaken by human splenocytes and stimulated spleen cells leading to expansion of T-cells.

  11. Sedimentation of nucleoids from thymus and spleen cells of rats after X-irradiation in vitro and in vivo

    International Nuclear Information System (INIS)

    Heinzelmann, R.

    1987-01-01

    The reaction to irradiation of thymocytes was tested immediately and 6 hours after whole body X-irradiation of rats with doses from 190 cGy up to 1520 cGy by nucleoid sedimentation. For comparison, examinations of thymus and spleen cells after X-irradiation in vitro were done. Preliminary analyses should find a possible coergism between X-rays on one side and hyperthermia and inhibitors of DNA-synthesis or DNA-repair (cytosinearabinoside, dideoxythymidine, 3-amino-benzamide, ethidiumbromide, and novobiocine) on the other side. From the results the following conclusions may be drawn: 1) With respect to the detection of in vivo effects of X-irradiation, the nucleoid sedimentation is less sensitive than biochemical methods. 2) Some hours after sublethal X-irradiation in vivo, free DNA and/or polydesoxyribonucleotides appear. At the same time cross-links can be detected in the chromatin fraction. 3) The reduction of the nucleoid sedimentation immediately after high doses of whole-body irradiation is the result of primary DNA lesions. The changes detectable some hours after are due to the secondary enzymatic changes, that are connected with the interphase death of thymocytes, and coincide with the present opinions about the irradiation induced apoptosis of cells. (orig./ECB) [de

  12. Characterization of nonlymphoid cells in rat spleen, with special reference to strongly Ia-positive branched cells in T-cell areas

    International Nuclear Information System (INIS)

    Dijkstra, C.D.

    1982-01-01

    By use of a monoclonal antibody against Ia antigen in an immunoperoxidase method, strongly Ia-positive branched cells are found in the T-cell areas of the splenic white pulp of the rat. In order to further characterize these cells, enzyme histochemical characteristics, phagocytic capacity, and irradiation sensitivity have been studied. Evidence is presented that these strongly Ia-positive branched cells represent interdigitating cells. The influence of whole-body irradiation on interdigitating cells is discussed. Comparison with data from the literature on the in vitro dendritic cell isolated from spleen cell suspensions reveals many similarities between the described interdigitating cell in vivo and the dendritic cell in vitro

  13. Differential antibody production by adherent and nonadherent spleen cells transferred to irradiated and cyclophosphamide-treated recipient mice

    International Nuclear Information System (INIS)

    Albright, J.F.; Deitchman, J.W.; Hassell, S.A.; Ozato, K.

    1975-01-01

    Mouse spleen cells were separated into adherent (Ad) and nonadherent (Nad) populations by incubation in plastic petri dishes. Adherent, Nad and unfractionated cell preparations (UCP) were transferred into syngeneic recipient mice that had been either irradiated or cyclophosphamide (CY) treated and the adoptive humoral Ab responses were studied by assessment of hemolytic Ab-forming cells (PFC) or humoral serum Ab production. Adherent cells failed to produce PFC in irradiated recipients, but functioned vigorously in CY-treated recipients. Nonadherent cells generated PFC in either type of host, as did UCP. Studies of comparative responses in CY-treated recipients revealed that: (a) Ad-cells generated 2 / 3 the number of PFC given by equivalent numbers of transferred Nad cells and UCP; (b) per equivalent numbers of transferred cells the Ad fraction generated 5 times more and 16 times more Ab than did the Nad cells and UCP, respectively. Spleen cells taken from mice 6 hr after CY treatment failed to respond to the mitogens phytohemagglutinin and bacterial lipopolysaccharide, showing that all cells were temporarily incapable of proliferation. Transfer of spleen cells from donor mice 16 hr after CY treatment, into thymectomized, irradiated, bone marrow-reconstituted recipients revealed substantial T-helper cell activity. We conclude that: (a) Ad preparations lacked T cells that were supplied by CY-treated recipients although T cell proliferation was temporarily inhibited in the latter; (b) B cells present in the Ad fraction were removed from some type of inhibitor of Ab synthesis and/or secretion, the production of which may be associated with T cells present in Nad preparations and UCP; (c) T-helper cells were only transiently affected by CY

  14. Sonographic assessment of spleen size in Saudi patients with sickle cell disease

    International Nuclear Information System (INIS)

    Al-Salem, Ahmed H.; Al-Aithan, S.; Al-Jama, A.; Al-Dabbous, I.; Bhamidipati, P.

    1998-01-01

    In patients with SCD, the spleen commonly enlarges during the first two decades of life but then undergoes autosplenectomy due to repeated attacks of vaso-occlusion and infarction. This, however, is not the case in Saudi patients with SCD (340 SCD and 23-sickle beta-thalassemia). A total of 363 patients were evaluated. There ages ranged from 1-60 years (mean 60 years). Only 24 (6.6%) of our patients had autosplenectomy. The splenic index increased with age until about 40 years of age and then gradually decreased indicating persistence of splenomegaly in our patients into an older age group. Forty-three patients (11.8%) had marked-massive splenomegaly (splenic index >120cm) and these had higher HbF levels (mean HbF=22.2%) when compared with those who had autosplenectomy (mean HbF=14.6). This is significant (P-value=0.0169) and confirms the effect of HbF on persistence of splenomegaly in SCD patients. Ultrasonography is a simple, safe and accurate method of assessing splenic size in patients with sickle cell disease. Patients with persistent splenomegaly should be followed closely for development of complications which may necessitate splenectomy. (author)

  15. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP10025–33 peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    International Nuclear Information System (INIS)

    Chang, Xiaoli; Xia, Chang-Qing

    2015-01-01

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100 25–33 peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100 25–33 peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100 25–33 peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100 25–33 were significantly increased compared to control groups. Tumor antigen, GP100 25–23 specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100 25–33 -coupled spleen cells leads to potent anti-melanoma immunity. • GP100 25–33 -coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  16. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP100{sub 25–33} peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiaoli [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL32610 (United States)

    2015-12-04

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100{sub 25–33} peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100{sub 25–33} peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100{sub 25–33} peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100{sub 25–33} were significantly increased compared to control groups. Tumor antigen, GP100{sub 25–23} specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100{sub 25–33}-coupled spleen cells leads to potent anti-melanoma immunity. • GP100{sub 25–33}-coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  17. Low-dose synergistic immunosuppression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in C57BL/6J murine spleen cells

    International Nuclear Information System (INIS)

    Li Qian; Lauer, Fredine T.; Liu Kejian; Hudson, Laurie G.; Burchiel, Scott W.

    2010-01-01

    Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both environmental agents that are known to have significant immunotoxicity. Previous studies have shown that PAH exposure of spleen cells in vitro produces significant immune suppression of humoral immunity, especially when P450 activation products are examined. Exposure to arsenic, particularly sodium arsenite, has also been found to be suppressive to antibody responses in vitro and in vivo. The purpose of the present studies was to examine the immunotoxicity of PAHs and arsenite following coexposures with the theory being that the agents may exert synergistic actions, which might be based on their different mechanisms of action. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic (arsenite or arsenate). Immunotoxicity assays were used to assess the T-dependent antibody response (TDAR) to sheep red blood cells (SRBCs), measured by a direct plaque-forming cell (PFC) assay. Cell viability was measured by trypan blue staining. Spleen cell viability was not altered following 4 days of PAH and/or arsenic treatment. However, the TDAR demonstrated suppression by both PAHs and arsenic in a concentration-dependent manner. p53 was also induced by NaAsO 2 (As 3+ ) and PAHs alone or in combination. The PAHs and their metabolites investigated included benzo[a]pyrene (BaP), BaP-7,8-diol, BaP-7,8-diol-9,10-epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression and inducing p53 expression. Interestingly, DB[a,l]P, a potent carcinogenic PAH not previously characterized for immunotoxicity, was also found to be strongly immunosuppressive. Arsenite (NaAsO 2 , As 3+ ) was found to produce immunosuppression at concentrations as low as 0.5 μM and was immunosuppressive at a 10-fold lower concentration than sodium arsenate (Na 2 HAsO 4 , As 5

  18. Recruitment of Gr1(+)CD11b (+)F4/80 (+) population in the bone marrow and spleen by irradiation-induced pulmonary damage.

    Science.gov (United States)

    Thanasegaran, Suganya; Ito, Sachiko; Nishio, Naomi; Uddin, Mohammad Nizam; Sun, Yang; Isobe, Ken-ichi

    2015-04-01

    Radiation-induced lung injury is a kind of sterile inflammation, which may lead to morbidity and mortality. The mechanism by which ionizing radiation activate the immune system is not well understood. In the present study, we have investigated the immunological responses induced by local irradiation-induced damage in mouse lung. The left lungs of C57BL/6 mice were irradiated at a high dose of 100 Gy. The histology of the lungs and spleen showed evidences of alveolar inflammation and congestion at 2 weeks after X-ray treatment. Also, prominent increase in cells expressing the cell surface markers, Gr(+)CD11b(+)F4/80(+) and Ly6C(+) Ly6G(+) were observed 2 weeks after X-ray treatment (100 Gy). Gr1(+)CD11b(+)F4/80(+) cell depletion by clodronate treatment reversed the histological effects and also failed to recruit Gr(+)CD11b(+) cells or F4/80(+) cells caused by irradiation. The origin of recruited Gr1(+)CD11b(+) cells was found to be a mixed resident and recruited phenotype.

  19. Kinetics of rebounding of lymphoid and myeloid cells in mouse peripheral blood, spleen and bone marrow after treatment with cyclophosphamide

    OpenAIRE

    Salem, Mohamed L.; Al-Khami, Amir A.; El-Nagaar, Sabry A.; Zidan, Abdel-Aziz A.; Al-Sharkawi, Ismail M.; Díaz-Montero, C. Marcela; Cole, David J.

    2012-01-01

    Recently, we showed that post cyclophosphamide (CTX) microenvironment benefits the function of transferred T cells. Analysis of the kinetics of cellular recovery after CTX treatment showed that a single 4 mg/mouse CTX treatment decreased the absolute number of leukocytes in the peripheral blood (PBL) at days 3-15, and in the spleen and bone marrow (BM) at days 3-6. The absolute numbers of CD11c+CD11b− and CD11c+CD11b+ dendritic cells (DCs), CD11b+ and Ly6G+ myeloid cells, T and B cells, CD4+C...

  20. Electrophoretic separation of cells and particles from rat pituitary and rat spleen

    Science.gov (United States)

    Hymer, Wesley C.

    1993-01-01

    There are 3 parts to the IML-2 TX-101 experiment. Part 1 is a pituitary cell culture experiment. Part 2 is a pituitary cell separation experiment using the Japanese free flow electrophoresis unit (FFEU). Part 3 is a pituitary secretory granule separation experiment using the FFEU. The objectives of this three part experiment are: (1) to determine the kinetics of production of biologically active growth hormone (GH) and prolactin (PRL) in rat pituitary GH and PRL cells in microgravity (micro-g); (2) to investigate three mechanisms by which a micro-g-induced lesion in hormone production may occur; and (3) to determine the quality of separations of pituitary cells and organelles by continuous flow electrophoresis (CFE) in micro-g under conditions where buoyancy-induced convection is eliminated.

  1. A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver.

    Science.gov (United States)

    Gotoh, Koro; Inoue, Megumi; Masaki, Takayuki; Chiba, Seiichi; Shimasaki, Takanobu; Ando, Hisae; Fujiwara, Kansuke; Katsuragi, Isao; Kakuma, Tetsuya; Seike, Masataka; Sakata, Toshiie; Yoshimatsu, Hironobu

    2012-08-01

    Obesity is associated with systemic low-grade inflammation and obesity-related metabolic disorders. Considering that obesity decreases the expression of proinflammatory cytokines in the spleen, we assessed the role of interleukin (IL)-10, an anti-inflammatory cytokine produced by the spleen, in the pathogenesis of obesity. Changes in obesity-related pathogenesis, including inflammatory responses in multiple organs, were assessed after systemic administration of exogenous IL-10 to splenectomy (SPX)-treated obese wild-type and IL-10 knockout (IL-10KO) mice. Obesity resulted in the inability of the spleen to synthesize cytokines, including IL-10, and proinflammatory cytokines in obesity are then likely to emerge from tissues other than the spleen because serum levels of IL-10, but not proinflammatory cytokines, decreased despite the expression of these cytokines in the spleen being reduced in high fat-induced obese mice. SPX aggravated the inflammatory response in white adipose tissue (WAT) and the liver and suppressed adiposity in WAT. However, it accentuated adiposity in the liver. These SPX-induced changes were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on the inflammatory responses in WAT and the liver of IL-10KO mice. These data show the role of spleen-derived IL-10 in diet-induced changes as a result of inflammatory responses in WAT and the liver.

  2. Selective accumulation of 147Pm in organism on induction of PCE's micronucleus and SCE of bone marrow cells as well as the chromosome aberrations on fetal liver and spleen

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Zheng Siying; Wang Liuyi; Lu Zhongyan; Yang Shuqin

    1989-01-01

    Study of accumulation peculiarity of 147 Pm showed that I.V. different doses of 147 Pm were the same selectively localized in skeleton and liver. Retention of 147 Pm in skeleton and liver was elevated when the radioactive doses of 147 Pm were increased. At the same time absorption does of 147 Pm radiation was heightened. The ability of 147 Pm to induce sister chromatid exchanges (SCEs) has been investigated by IdU labelling methods. A statistically significant elevation of SCEs was observed after 147 Pm intake.In mice the number of SCEs per cell in bone marrow cells was always higher when the animals were maintained on the doses of 37 Bq/g. The injurious effects of 147 Pm, using PCE's micronucleus rates in bone marrow cells were observed. 147 Pm was dominantly deposited on maternal liver. Deposition of 147 Pm in maternal spleen was about quandrantal of the maternal liver. Studies indicated that maternal contamination of 147 Pm could induced chromosome aberrations in fetal liver and spleen cells. Among the type of aberrations induced by 147 Pm, chromatid breakage were predominant. The incidence of chromosome aberrations on fetal liver cells induced by 147 Pm was higher on fetal spleen cells

  3. Induced prion protein controls immune-activated retroviruses in the mouse spleen.

    Directory of Open Access Journals (Sweden)

    Marius Lötscher

    Full Text Available The prion protein (PrP is crucially involved in transmissible spongiform encephalopathies (TSE, but neither its exact role in disease nor its physiological function are known. Here we show for mice, using histological, immunochemical and PCR-based methods, that stimulation of innate resistance was followed by appearance of numerous endogenous retroviruses and ensuing PrP up-regulation in germinal centers of the spleen. Subsequently, the activated retroviruses disappeared in a PrP-dependent manner. Our results reveal the regular involvement of endogenous retroviruses in murine immune responses and provide evidence for an essential function of PrP in the control of the retroviral activity. The interaction between PrP and ubiquitous endogenous retroviruses may allow new interpretations of TSE pathophysiology and explain the evolutionary conservation of PrP.

  4. The bovine spleen: Interactions among splenic cell populations in the innate immunologic control of hemoparasitic infections

    Science.gov (United States)

    Over the past several years, innate immunity has been recognized as having an important role as a front-line defense mechanism and as an integral part of the adaptive immune response. Innate immunity in cattle exposed to hemoparasites is spleen-dependent and age-related. In this review, we discuss g...

  5. Dendritic Cells from Peyer's Patches and Mesenteric Lymph Nodes Differ from Spleen Dendritic Cells in their Response to Commensal Gut Bacteria

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Frøkiær, Hanne

    2008-01-01

    . Expression of CCR7 and CD103 on the surface of MLN DC, necessary for the induction of gut-homing regulatory T cells, increased with stimulation by Gram-positive commensals. Bacteria-dependent cytokine production (IL-6, IL-10 and TNF-alpha) was similar in spleen and MLN DC, and contaminant cells in these DC...

  6. Immunization with PIII, a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, affects nitric oxide production by murine spleen cells

    Directory of Open Access Journals (Sweden)

    Diana Magalhães de Oliveira

    1998-01-01

    Full Text Available Nitric oxide (NO is an important effector molecule involved in immune regulation and defense. NO produced by cytokine-activated macrophages was reported to be cytotoxic against the helminth Schistosoma mansoni. Identification and characterization of S. mansoni antigens that can provide protective immunity is crucial for understanding the complex immunoregulatory events that modulate the immune response in schistosomiasis. It is, then, essential to have available defined, purified parasite antigens. Previous work by our laboratory identified a fraction of S. mansoni soluble adult worm antigenic preparation (SWAP, named PIII, able to elicit significant in vitro cell proliferation and at the same time lower in vitro and in vivo granuloma formation when compared either to SEA (soluble egg antigen or to SWAP. In the present work we report the effect of different in vivo trials with mice on their spleen cells ability to produce NO. We demonstrate that PIII-immunization is able to significantly increase NO production by spleen cells after in vitro stimulation with LPS. These data suggest a possible role for NO on the protective immunity induced by PIII.

  7. The effect of whole body or total-head x irradiation of the metallophilic cells in the mice spleen

    International Nuclear Information System (INIS)

    Sasaki, Osamu; Matsueda, Yasutoshi; Mizuguchi, Hiroshi; Moriguchi, Kenzo; Ogata, Kunitoshi; Sugie, Tsuneto

    1984-01-01

    The purpose of this paper is to clarify morphological changes of the reticuloendothelial cells in the spleen following X-irradiation by Katsura's silver impregnation method. The animals used in this experiment were ddN female mice weighing 20 to 25g. The mice were given X-irradiation to the total-head (1,500R) or whole body (300R). The metallophilic cells in the spleen of control mice were of the small foamy type in the follicle, the large stellate type in the marginal metallophils, the small branching type in the marginal zone and the small foamy or round type in the red pulp, respectively. The metallophilic cells decreased immediately after whole body irradiation and the number of cells returned to normal in from 10 to 14 days. On the other hand, the number of the metallophilic cells in the follicle and the perifollicular region increased immediately after total-head X-irradiation. This state continued for several days. In the marginal zone and red pulp, the number of amoebian type cells appeared from 24 hours after irradiation and the number of cells in total-head irradiation group were more clearly distinguishable than in the whole body irradiated group. (author)

  8. Murine neonatal spleen contains natural T and non-T suppressor cells capable of inhibiting adult alloreactive and newborn autoreactive T-cell proliferation.

    Science.gov (United States)

    Hooper, D C; Hoskin, D W; Gronvik, K O; Murgita, R A

    1986-05-01

    The spleen of neonatal mice is known to be a rich source of cells capable of suppressing a variety of immune functions of adult lymphocytes in vitro. From such observations has emerged the concept that the gradual development in ability to express immune functions after birth is due in part to the parallel normal physiological decay of naturally occurring regulatory suppressor cells. There is, however, some confusion in the literature as to the exact nature of the newborn of the newborn inhibitory cell type(s). In contrast to most previous reports which detect only a single type of neonatal suppressor cell, usually a T cell, we show here that newborn spleen harbors both T and non-T inhibitory cells. Both types of suppressor cells could be shown to suppress the proliferative response of adult spleen to alloantigens as well as newborn T cells reacting against self-Ia antigen in the autologous mixed lymphocyte reaction (AMLR). Newborn suppressor T cells were characterized as being non-adherent to Ig-anti-Ig affinity columns, soybean agglutinin receptor negative (SBA-), and susceptible to lysis by anti-T-cell specific antiserum plus complement. Non-T suppressor cells were identified as non-phagocytic, SBA receptor positive (SBA+), and resistant to cytotoxic treatment with anti-T-cell antibodies and complement. The apparent controversy surrounding previous reports as to the T versus non-T nature of newborn suppressor cells can be reconciled by the present observation that both types of inhibitory cells coexist in the spleen. Furthermore, the demonstration that newborn suppressor cells can effectively regulate T-cell proliferative activity mediated by other newborn cells provides more direct support for the contention that such inhibitory cells play a physiological role in controlling immune responsiveness during early ontogeny.

  9. α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way

    Directory of Open Access Journals (Sweden)

    Andrea Grandi

    2017-11-01

    Full Text Available The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α7 nAChRs stimulation is still controversial and the potential contribution of α4β2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α7 and α4β2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403 and antagonists (methyllycaconitine and dihydro-β-erythroidine of α7 and α4β2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α4β2 ligands evoked weak and contradictory effects, while α7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune

  10. Alkaline phosphatase role in bone marrow and spleen hemopoietic cells recovery after mouse whole-body irradiation

    International Nuclear Information System (INIS)

    Al Mouhamad, K.; Al Sheikh, F.

    2013-04-01

    Hematopoietic tissue is consisted of two distinctly different tissues, the first part is the hematopoietic stem cells and the second tissue is a mixture of many supportive cells which the most important one of them is alkaline phosphatase (ALP)-secreted-fibroblastic cells (FBCs). It was thought that FBCs play an important role in the hematopoiesis through ALP secretion. Our previous studies indicated that the ALP secretion in bone marrow (BM) increased after a whole mouse body irradiation when the BM cellular component is completely destroyed and, then it was decreased when the BM regain its cellular component. We performed some experiences to verify if there is any role to the ALP in the hematopoiesis. We irradiated three groups of mice to non-lethal dose, the first one was injected by Tetramizole (anti-ALP) 24 hours before irradiation, and the second was injected by Lisinopril (anti-hematopoiesis) 24 hours before irradiation and the third left without any injection. The fourth left as control. Many histological sections were taken from BM and spleen on 1, 3, 7 and 30 days after irradiation to perform ALP-histological detection. These experiences were repeated to count BM cells. ALP secretion level in the BM was reached the maximum 3 days after irradiation without any injection when the cell number was in minimum then, the level of ALP start to decrease and the cell number start to increase. ALP secretion delayed when the mice were injected by Tetramizole and BM cell population also delayed to return to its normal position. But, the ALP secretion increased directly after irradiation when the mice were injected by Lisinopril which, the ALP secretion, normally reached the maximum by the third day. These results may indicate a role to the ALP in BM and spleen hematopoietic cell recovery (author).

  11. Correlation of ultrasound findings, liver and spleen cytology, and prognosis in the clinical staging of high metastatic risk canine mast cell tumors.

    Science.gov (United States)

    Book, Alison P; Fidel, Janean; Wills, Tamara; Bryan, Jeffrey; Sellon, Rance; Mattoon, John

    2011-01-01

    Cytologic sampling of the ultrasonographically normal spleen and liver is not implemented routinely in the clinical staging of canine cutaneous mast cell tumors and normal ultrasound findings are often accepted as sufficient evidence for ruling out splenic or liver metastasis. Our objective was to define the specificity and sensitivity of ultrasound findings for diagnosis of mast cell infiltration when verified with cytologic evaluation, and to define the prognostic role of cytologic evaluation of liver and splenic aspirates. Dogs with a diagnosis of clinically aggressive grade II, or grade III mast cell tumor treated with a combination vinblastine/CCNU chemotherapy protocol, were selected retrospectively based on availability of cytologic evaluation of spleen plus or minus liver for staging. Out of 19 dogs, 10 dogs had a grade II tumor and nine a grade III tumor. Seven dogs had mast cell infiltration of the spleen, liver, or both. The sensitivity of ultrasound for detecting mast cell infiltration was 43% for the spleen and 0% for the liver. Dogs with positive cytologic evidence of mast cell infiltration to spleen, liver, or both had significantly shorter survival (100 vs. 291 days) than dogs without evidence of mast cell infiltration (Pdogs with a clinically aggressive mast cell tumor. © 2011 Veterinary Radiology & Ultrasound.

  12. Intrathymic T cell differentiation in radiation bone marrow chimeras and its role in T cell emigration to the spleen. An immunohistochemical study

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.; Kubo, S.; Kamisaku, H.; Hitomi, K.; Utsuyama, M.

    1985-01-01

    Immunohistochemical studies were made on the regeneration of T cells of host- and donor-type in the thymus and spleen of radiation bone marrow chimeras by using B10- and B10.BR-Thy-1 congenic mice. In Thy-1 congenic chimeras, thymocytes of donor bone marrow origin, were first recognized at day 7, when the thymus involuted to the smallest size after the irradiation. The thymocytes of donor-type then proliferated exponentially, showing a slightly faster rate when higher doses of bone marrow cells were used for reconstitution, reaching a level of 100 million by day 17 and completely replacing the cortical thymocytes of host origin by day 21. The replacement of medullary thymocytes from host- to donor-type occurred gradually between days 21 and 35, after the replacement in the cortex was completed. In the spleen, about 1 million survived cells were recovered at day 3 after the irradiation, and approximately 60% of them were shown to be host-type T cells that were observed in the white pulp areas. The host-type T cells in the spleen increased gradually after day 10, due to the influx of host-type T cells from the regenerating thymus. Thus a pronounced increase of T cells of host-type was immunohistochemically observed in the splenic white pulp between days 21 and 28, when thymocytes of host-type were present mainly in the thymic medulla. These host-type T cells were shown to persist in the spleen for a long time, as long as 420 days after the treatment. Phenotypically, they were predominantly Lyt-1+2+ when examined at day 28, but 5 mo later, they were about 50% Lyt-1+2+ and 50% Lyt-1+2-

  13. Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease.

    Directory of Open Access Journals (Sweden)

    Koro Gotoh

    Full Text Available Obesity is associated with systemic low-grade inflammation and is a risk factor for non-alcoholic fatty pancreas disease (NAFPD, but the molecular mechanisms of these associations are not clear. Interleukin (IL-10, a potent anti-inflammatory cytokine, is released during acute pancreatitis and is known to limit inflammatory responses by downregulating the release of proinflammatory mediators. The origin of IL-10 that suppresses pancreatitis has not been investigated. Since obesity is known to reduce expression of proinflammatory cytokines in the spleen, we examined whether spleen-derived IL-10 regulates NAFPD caused by high-fat (HF diet-induced obesity. The following investigations were performed: 1 IL-10 induction from spleen was examined in male mice fed a HF diet; 2 triglyceride content, expression of pro- and anti-inflammatory cytokines and infiltration of M1 and M2 macrophages were determined to evaluate ectopic fat accumulation and inflammatory responses in the pancreas of splenectomy (SPX-treated mice fed HF diet; 3 exogenous IL-10 was systemically administered to SPX-treated obese mice and the resulting pathogenesis caused by SPX was assessed; and 4 IL-10 knockout (IL-10KO mice were treated with SPX and ectopic fat deposition and inflammatory conditions in the pancreas were investigated. Obesity impaired the ability of the spleen to synthesize cytokines, including IL-10. SPX aggravated fat accumulation and inflammatory responses in the pancreas of HF diet-induced obese mice and these effects were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on fat deposition and inflammatory responses in the pancreas of IL-10KO mice. Our findings indicate that obesity reduces IL-10 production by the spleen and that spleen-derived IL-10 may protect against the development of NAFPD.

  14. Splenectomy exacerbates atrial inflammatory fibrosis and vulnerability to atrial fibrillation induced by pressure overload in rats: Possible role of spleen-derived interleukin-10.

    Science.gov (United States)

    Kondo, Hidekazu; Takahashi, Naohiko; Gotoh, Koro; Fukui, Akira; Saito, Shotaro; Aoki, Kohei; Kume, Osamu; Shinohara, Tetsuji; Teshima, Yasushi; Saikawa, Tetsunori

    2016-01-01

    The spleen is important for cardiac remodeling induced by myocardial infarction. However, the role of the spleen in inflammatory atrial fibrosis induced by pressure overload is unknown. The purpose of this study was to investigate whether splenectomy (SPX) attenuates or exacerbates pressure overload-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in rats. Male Sprague-Dawley rats (6 weeks old) were divided into Sham+Sham, Sham+SPX, abdominal aortic constriction (AAC)+Sham, and AAC+SPX groups, and were evaluated for inflammation, fibrosis, and AF on days 2, 4, 14, and 28. On day 4, an AAC-induced rise in interleukin-10 (IL-10) level was observed in the spleen, serum, and left atrium (LA), with SPX showing inhibitory effects in the latter 2 instances. In addition, AAC-induced M2 macrophage recruitment into the LA was decreased by SPX, as determined by immunofluorescence labeling (P <.05). On day 28, AAC-induced heterogeneous interstitial fibrosis of the LA was enhanced by SPX (P <.05). Electrophysiologic recordings revealed that the duration of AF and prolongation of interatrial conduction time induced by AAC were increased by SPX (P < .01 and P <.05, respectively). Furthermore, in the AAC+SPX group, the number of macrophages infiltrating into the LA on day 2 was marginal, but increased on day 28 relative to the AAC+Sham group. IL-10 administration attenuated the AAC-induced atrial remodeling that was aggravated by SPX. The study results suggest that SPX exacerbates AAC-induced inflammatory atrial fibrosis and increases vulnerability to AF after 4 weeks, likely because of depletion of spleen-derived IL-10. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  15. Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient.

    Science.gov (United States)

    Lee, Hye Kyung; Kim, Hee Jung; Lee, Eun Hee; Kim, Suk Young; Park, Tae In; Kang, Chang Suk; Yang, Woo Ick

    2003-01-01

    The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity. PMID:12692428

  16. Littoral cell angioma of the spleen in a patient with previous pulmonary sarcoidosis: a TNF-α related pathogenesis?

    Directory of Open Access Journals (Sweden)

    Titze Ulf

    2011-09-01

    Full Text Available Abstract Background Littoral cell angioma (LCA is a rare vascular tumor of the spleen. Generally thought to be benign, additional cases of LCA with malignant features have been described. Thus, its malignant potential seems to vary and must be considered uncertain. The etiology remains unclear, but an immune dysregulation for the apparent association with malignancies of visceral organs or immune-mediated diseases has been proposed. Case Presentation We report a case of LCA in a 43-year old male patient who presented with a loss of appetite and intermittent upper abdominal pain. Computed tomography showed multiple hypoattenuating splenic lesions which were hyperechogenic on abdominal ultrasound. Lymphoma was presumed and splenectomy was performed. Pathological evaluation revealed LCA. Conclusions LCA is a rare, primary vascular neoplasm of the spleen that might etiologically be associated with immune dysregulation. In addition, it shows a striking association with synchronous or prior malignancies. With about one-third of the reported cases to date being co-existent with malignancies of visceral organs or immune-mediated diseases, this advocates for close follow-ups in all patients diagnosed with LCA. To our knowledge, this report is the first one of LCA associated with previous pulmonary sarcoidosis and hypothesizes a TNF-α related pathogenesis of this splenic tumor.

  17. Leukemic transformation of donor spleen cells following their transplantation into supralethally irradiated mice with pre-existing viral leukemia. [X Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnert, P M; OKunewick, J P; Erhard, P

    1974-01-01

    Fialkow et al. previously reported leukemia induction in donor-type cells after treating patients for acute lymphoblastic leukemia with total-body irradiation and hematopoietic cell transplantation. Utilizing a murine model and paralleling their treatment protocol, we have documented that induction of leukemia can occur in normal donor cells transplanted into Rauscher viral leukemic mice at 0, 1 and 2 days after irradiation. The induction of leukemia in the grafted cells was verified by: the occurrence of splenomegaly; and secondary spleen cell transplants, whereby the secondary donors were transplanted mice still alive at 30 days and the secondary recipients were normal unirradiated mice. The spleen weights of the grafted leukemic mice were found to be significantly greater than those of the controls and all secondary recipients that received spleen cells from the primary grafted leukemic mice also died of leukemia. Verification that the regenerating hematopoietic tissue was from donor (males) and not host source (females) was accomplished by spleen chromosome preparations taken from randomly selected mice at 14 and at 30 days after cell transplantation. In these preparations, the Y chromosome was clearly distinguishable on the basis of size, shape, and differential staining. The data indicate that induction of leukemia after whole-body irradiation and hematopoietic cell transplantation can occur in immunologically matched donor cells when a viral agent is present and that the incidence of this induction is not affected by a time delay between irradiation and transplant.

  18. Dectin-1-mediated signaling leads to characteristic gene expressions and cytokine secretion via spleen tyrosine kinase (Syk) in rat mast cells.

    Science.gov (United States)

    Kimura, Yukihiro; Chihara, Kazuyasu; Honjoh, Chisato; Takeuchi, Kenji; Yamauchi, Shota; Yoshiki, Hatsumi; Fujieda, Shigeharu; Sada, Kiyonao

    2014-11-07

    Dectin-1 recognizes β-glucan and plays important roles for the antifungal immunity through the activation of spleen tyrosine kinase (Syk) in dendritic cells or macrophages. Recently, expression of Dectin-1 was also identified in human and mouse mast cells, although its physiological roles were largely unknown. In this report, rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Treatment of cells with Dectin-1-specific agonist curdlan induced tyrosine phosphorylation of cellular proteins and the interaction of Dectin-1 with the Src homology 2 domain of Syk. These responses depended on tyrosine phosphorylation of the hemi-immunoreceptor tyrosine-based activation motif in the cytoplasmic tail of Dectin-1, whereas they were independent of the γ-subunit of high-affinity IgE receptor. DNA microarray and real-time PCR analyses showed that Dectin-1-mediated signaling stimulated gene expression of transcription factor Nfkbiz and inflammatory cytokines, such as monocyte chemoattractant protein-1, IL-3, IL-4, IL-13, and tumor necrosis factor (TNF)-α. The response was abrogated by pretreatment with Syk inhibitor R406. These results suggest that Syk is critical for Dectin-1-mediated activation of mast cells, although the signaling differs from that triggered by FcϵRI activation. In addition, these gene expressions induced by curdlan stimulation were specifically observed in mast cells, suggesting that Dectin-1-mediated signaling of mast cells offers new insight into the antifungal immunity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Comparison of the suppressor cells found in the spleens of 89Sr-treated mice and in normal murine bone marrow

    International Nuclear Information System (INIS)

    Levy, E.M.; Corvese, J.S.; Bennett, M.

    1981-01-01

    Normal murine bone marrow cells and spleen cells of mice treated with 89 Sr both have suppressive activity. These nonspecific suppressor cells inhibit the ability of normal spleen cells to undergo antibody responses in vitro. After being precultured for 24 hr, these cells will also suppress antibody responses in vivo and the responses of normal spleen cells to T and B cell mitogens in vitro. These cells have previously been shown not to be mature T or B lymphocytes or macrophages. Velocity sedimentation and cell-size analysis indicated that both suppressor cells are large (approx. =206 μ 3 ). Mitomycin C treatment eliminated the ability of both suppressor cells to inhibit an in vitro antibody response. In contrast, this treatment did not reduce the ability of the cells to inhibit an in vitro antibody response. In contrast, this treatment did not reduce the ability of the cells to suppress a mitogenic response. Irradiation (1000 R) was also ineffective in eliminating the ability of either cell to suppress a mitogenic response. We conclude that the 2 suppressor cells are closely related if not identical, and we speculate that these cells may function in vivo to suppress immune reactivity in areas of intense hematopoiesis

  20. Age-related increase in the rate of spontaneou and γ-ray-induced hprt mutations in mouse spleen lymphocytes

    International Nuclear Information System (INIS)

    Gazlev, A.I.; Podlutskii, A.Ya.; Bradbury, R.

    1994-01-01

    Endogenous and exogenous factors continually afflict DNA of cells of organisms. A certain amount of the damage is accumulated causing mutations, increasing the risk of malignacies, impairing cell functions, and upsetting the body's homeostasis. The research reported here studies the rates of spontaneous hprt nmutationsand those induced you ggammairradiation in the splenocytes of mice at various ages. The rate of spontaneous and induced hprt gene mutations increases with aging. In gamma irradiated mice the rate of radiation-induced mutations depended on the absorbed dose and age, with the rate 2.3-3.0 fold higher in 104-110 week old mice than in younger pups. 15 refs., 1 tab

  1. Comparison of altered expression of histocompatibility antigens with altered immune function in murine spleen cells treated with ultraviolet radiation and/or TPA

    International Nuclear Information System (INIS)

    Pretell, J.O.; Cone, R.E.

    1985-01-01

    Previous studies in our laboratory demonstrated that several treatments that inhibited the ability of cells to stimulate the mixed lymphocyte reaction (MLR) also blocked the shedding of histocompatibility antigens and Ia antigens from murine spleen cells. In the present studies, one of these treatments, ultraviolet radiation (UV), was shown to cause an initial loss in the density of H-2K, IA, and IE antigens prior to the block in shedding observed after culture of these cells. Further analysis revealed that the UV-induced loss of antigens could be prevented by the presence of colchicine during irradiation. Biosynthetic analyses revealed the IA antigen synthesis was also inhibited in the UV-irradiated cells. Examination of the effects of a second agent, 12-0-tetradecanoylphorbol-13-acetate (TPA) on the turnover of histocompatibility antigens revealed that the biosynthesis and shedding of these antigens were accelerated by this agent. However, addition of TPA to UV-irradiated cells did not result in a reversal of the UV-induced block in biosynthesis of IA antigens. Results of immune function assays correlated with the biochemical studies: UV-irradiation inhibited the generation of the MLR, but TPA enhanced this reaction, and addition of TPA to mixed lymphocyte cultures with UV-irradiated stimulators did not reverse the UV-induced inhibition. These results suggest that, although the turnover of histocompatibility antigens may be affected by TPA and UV in an antagonistic fashion, additional factors other than the expression of histocompatibility antigens are operating in the inhibition of stimulation of an MLR by UV radiation or its enhancement by TPA

  2. 99 mTc-sulphur-colloid and heat-denatured 99mTc-labelled red cell scans demonstrating a giant intrapelvic spleen in a girl after splenectomy

    International Nuclear Information System (INIS)

    Kao, P.F.; Tzen, K.Y.; Tsai, M.F.; Lin, J.N.

    2001-01-01

    A 17 x 12 x 5-cm giant intrapelvic mass in a 14-year-old girl is reported. This mass developed 6 years after a splenectomy for splenic torsion. The heat-denatured 99 m Tc-labelled red cell scan and 99 m Tc- sulphur-colloid scan confirmed the specific red cell sequestration function and reticuloendothelial activity in the giant intrapelvic spleen. The size and development of the giant intrapelvic spleen are unusual. The usefulness of functional images to diagnosis the nature of the intrapelvic mass is well demonstrated. (orig.)

  3. Contrasting feature in the repopulation of host-type T cells in the spleens of F1----P and P----F1 radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.; Kubo, S.; Kamisaku, H.; Utsuyama, M.

    1986-01-01

    The regeneration and persistence of host- and donor-derived T cells were examined in the thymus as well as the spleen of mouse radiation bone marrow chimeras of two semiallogeneic combinations (F1----P, P----F1) with different Thy-1 markers on T cells of donor and host origins. An unexpectedly large number of host-type T cells were recovered from the spleens of F1----P chimeras, amounting to as high as 45 and 25% of total T cells at 6 and 14 weeks after bone marrow transplantation (BMT), respectively. To the contrary, the residual host-type T cells in the spleens of P----F1 chimeras disappeared quickly, resulting in less than 0.1% of total T cells at 6 weeks after BMT. It was also revealed that the number of host-type T cells in the spleens of F1----P chimeras decreased in proportion to increase of radiation dose given to the recipients

  4. Comparative investigations about the DNA synthesis by thymus and spleen cells of rats in vitro under the influence of X-rays, UV radiation and radiomimetic substances

    Energy Technology Data Exchange (ETDEWEB)

    Tempel, K.; Schmerold, I.; Pfahler, W.; Goette, A.

    1984-06-01

    In order to further characterize the different repairing behavior of thymus and spleen cells of rats in vitro under the influence of X-rays, UV radiation and methylmethanesulfonate (MMS), the effect of bleomycine (BM), L-cysteine (CY-E), N-ethylmaleimide (NEM), I-..beta..-D-arabinofuranosylcytosine (araC), dideoxythymidine (ddT), and novobiocine (NB) on the semiconservative and restorative DNA synthesis as well as on the behavior of DNA under the alkaline elution was studied. The semiconservative DNA synthesis was inhibited by all examined agents except ddT, the restorative DNA synthesis only by NEM, araC, and NB. The stimulation of the restorative DNA synthesis was increased by UV radiation and MMS in spleen cells and by X-rays, BM and CY-E in thymus cells. Under the conditions of alkaline elution, there was a more sensitive reaction of spleen cells than of thymus cells to X-rays, BM and CY-E. The results show that thymus cells are especially qualified for the repair of short chains and spleen cells for the repair of long chains.

  5. The Spleen: A forgotten organ

    International Nuclear Information System (INIS)

    Castrillon German; Montoya Maria del Pilar; Echeverri Santiago

    2010-01-01

    The spleen has traditionally been regarded as an orphan organ. Its embryological development is described together with the digestive system, although it is not part of the gastrointestinal tract. Its main function is during the early fetal development when it produces both red and white blood cells, losing this function during the late fetal life. Nevertheless, the spleen continues to work as a filter for blood cells and also has important immune functions. As it is not necessary for the preservation of vital life functions, the spleen receives limited attention by both radiologists and clinicians. It is, however, an organ with multiple pathological conditions that have representation in the different diagnostic imaging modalities; radiologists, therefore, must be aware of these conditions and their radiological characteristics. This article provides a diagnostic approach to the most common diseases affecting the spleen using tomography and magnetic resonance.

  6. Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo [KAERI, Taejon (Korea)

    2003-10-01

    This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation.

  7. Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

    International Nuclear Information System (INIS)

    Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo

    2003-01-01

    This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation

  8. Comparative Ultrastructure of Langerhans-Like Cells in Spleens of Ray-Finned Fishes (Actinopterygii)

    Czech Academy of Sciences Publication Activity Database

    Lovy, J.; Wright, G. M.; Speare, D. J.; Tyml, Tomáš; Dyková, Iva

    2010-01-01

    Roč. 271, č. 10 (2010), s. 1229-1239 ISSN 0362-2525 R&D Projects: GA MŠk LC522 Institutional research plan: CEZ:AV0Z60220518 Keywords : fish * cyprinidae * halibut * dendritic cells * Langerhans cell * Birbeck granules * ultrastructure Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 1.773, year: 2010

  9. Hybridization change of DNA and nuclear RNA synthesized immediately after ionizing irradiation in spleen cells isolated from 615 mice

    International Nuclear Information System (INIS)

    Meng Ziqiang

    1986-01-01

    DNA hybridization with nuclear RNA(nRNA) synthesized immediately after 60 Co Gamma-irradiation in the spleen cells freshly isolated from inbred line 615 mice was investigated, using the technique of Gillespie and Spiegelman. In RNA/DNA hybridization percentage experiment, it was showed that the hybridization of normal DNA with labelled nRNA synthesized in irradiated cells reached the saturation point at a much faster rate than with labelled normal nRNA. The hybridization percentage of nRNA synthesized in irradiated cells was higher than that of normal nRNA during the different reaction time before the saturation point of DNA with nRNA synthesized in irradiated cells, but it was lower than that of normal nRNA after the zone of high repetitive DNA sequences was stimulated, however, the transcription of some base sequences in the zone of low repetitive DNA sequences was seriously inhibited. Measurements of the exhaustion rates of pulse-labelled nRNA were carried out as described by Greene and Flickinger Biochim. In these studies, pulse-labelled nRNA synthesized in unirradiated and irradiated cells were compared by exhausion with DNA at hybridization time of 4 or 24 hours, When the hybridization time was 4 hours, the nRNA synthesized in irradiated cells displayed a faster exhaustion rate than the control nRNA. But if the hybridization time was 24 hours, the exhaustion rate of nRNA synthesized in irradiated cells reduced. These results demostrated that Gamma-irradiation changed the proportion of transcription of some nRNA species and implayed that the sensitivities of the transcription activeties of the different repetitive DNA sequences to Gamma-irradiation were different, and so were the transcription activeties of the different base sequences in the same repetitive DNA sequences

  10. Radiosensitivity of hemopoietic stem cells on cloning in bone marrow and spleen

    International Nuclear Information System (INIS)

    Shvets, V.N.; Shafirkin, A.V.

    1979-01-01

    It was shown that population of stem cells from bone marrow of mice is heterogenous by radiosensitivity. A 55%-survival of CFU is exponential function of radiation dose (D 0 -9 rad). A dose-effect curve for radioresistant part of the population (D 0 =180 rad) is sygmoid (Dsub(q)=130 rad). Radiosensitive CFU are suggested to represent a primarily committed fraction of half-semi cells, and radioresistant CFU are referable to a pool of pluripotent stem cells. Heterogenous nature of CFU population is proved with different modifications of radiation effect and interactions of CFU with T-lymphocytes

  11. Immunity to Babesia in mice I. Adoptive transfer of immunity to Babesia rodhaini with immune spleen cells and the effect of irradiation on the protection of immune mice

    NARCIS (Netherlands)

    Kuil, H.; Zivkovic, D.; Seinen, W.; Albers-van Bemmel, C.M.G.; Speksnijder, J.E.

    1984-01-01

    Immunisation of Balb/c mice against Babesia rodhaini by an amicarbalide- controlled infection resulted in a solid immunity which lasted for 216 days. With spleen cells of immune mice protection could be transferred both to naive mice pretreated with cyclophosphamide. Treatment of naive mice with

  12. Pediatric littoral cell angioma of the spleen: multimodality imaging including diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M. [Johns Hopkins Hospital, Division of Pediatric Radiology, Department of Radiology and Radiological Science, Baltimore, MD (United States); Mitchell, Sally [Johns Hopkins Hospital, Division of Cardiovascular and Interventional Radiology, Department of Radiology and Radiological Science, Baltimore (United States); Keefer, Jeffrey [Johns Hopkins Hospital, Division of Pediatric Hematology, Department of Pediatrics, Baltimore, MD (United States)

    2009-10-15

    Littoral cell angioma (LCA) is a rare primary splenic vascular tumor originating from littoral cells lining the splenic red pulp sinuses. LCAs are rarely seen in children. We present the US, CT, and MRI findings including diffusion-weighted imaging (DWI) in a 2-year-old boy with histologically proven LCA. Previous studies on liver lesions have shown that DWI allows differentiation of vascular tumors from primary neoplasms and metastatic disease. The current case indicates that increased ADC values within the splenic lesions suggest a vascular etiology, which might help narrow the differential diagnosis. (orig.)

  13. Pediatric littoral cell angioma of the spleen: multimodality imaging including diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M.; Mitchell, Sally; Keefer, Jeffrey

    2009-01-01

    Littoral cell angioma (LCA) is a rare primary splenic vascular tumor originating from littoral cells lining the splenic red pulp sinuses. LCAs are rarely seen in children. We present the US, CT, and MRI findings including diffusion-weighted imaging (DWI) in a 2-year-old boy with histologically proven LCA. Previous studies on liver lesions have shown that DWI allows differentiation of vascular tumors from primary neoplasms and metastatic disease. The current case indicates that increased ADC values within the splenic lesions suggest a vascular etiology, which might help narrow the differential diagnosis. (orig.)

  14. The influence of some prostaglandins on DNA synthesis and DNA excision repair in mouse spleen cells ''in vitro''

    International Nuclear Information System (INIS)

    Klein, W.; Altmann, H.; Kocsis, F.; Egg, D.; Guenther, R.

    1978-03-01

    ''In vitro'' experiments were performed on mouse spleen cells to establish possible influences of some naturally occurring prostaglandins on DNA synthesis and DNA excision repair. The prostaglandins A 1 , B 1 , E 1 , E 2 and Fsub(2α) were tested in concentrations of 10 pg, 5 ng and 2,5μg per ml cell suspension. DNA synthesis was significantly increased by PgFsub(2α) in all the three concentrations tested, while the other tested prostaglandins were essentially ineffective. DNA excision repair was significantly inhibited by PgE 1 and PgE 2 at 5 ng/ml and at 2,5 μg/ml but increased by PgFsub(2α) in the two lower concentrations. The rejoining of DNA-strand breaks after gamma-irradiation was slightly reduced by PgE 1 , PgE 2 and PgF 2 at 2,5 μg/ml. (author)

  15. Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system.

    Science.gov (United States)

    Krebber, A; Bornhauser, S; Burmester, J; Honegger, A; Willuda, J; Bosshard, H R; Plückthun, A

    1997-02-14

    A prerequisite for the use of recombinant antibody technologies starting from hybridomas or immune repertoires is the reliable cloning of functional immunoglobulin genes. For this purpose, a standard phage display system was optimized for robustness, vector stability, tight control of scFv-delta geneIII expression, primer usage for PCR amplification of variable region genes, scFv assembly strategy and subsequent directional cloning using a single rare cutting restriction enzyme. This integrated cloning, screening and selection system allowed us to rapidly obtain antigen binding scFvs derived from spleen-cell repertoires of mice immunized with ampicillin as well as from all hybridoma cell lines tested to date. As representative examples, cloning of monoclonal antibodies against a his tag, leucine zippers, the tumor marker EGP-2 and the insecticide DDT is presented. Several hybridomas whose genes could not be cloned in previous experimental setups, but were successfully obtained with the present system, expressed high amounts of aberrant heavy and light chain mRNAs, which were amplified by PCR and greatly exceeded the amount of binding antibody sequences. These contaminating variable region genes were successfully eliminated by employing the optimized phage display system, thus avoiding time consuming sequencing of non-binding scFv genes. To maximize soluble expression of functional scFvs subsequent to cloning, a compatible vector series to simplify modification, detection, multimerization and rapid purification of recombinant antibody fragments was constructed.

  16. CD11c-positive cells from brain, spleen, lung, and liver exhibit site-specific immune phenotypes and plastically adapt to new environments.

    Science.gov (United States)

    Immig, Kerstin; Gericke, Martin; Menzel, Franziska; Merz, Felicitas; Krueger, Martin; Schiefenhövel, Fridtjof; Lösche, Andreas; Jäger, Kathrin; Hanisch, Uwe-Karsten; Biber, Knut; Bechmann, Ingo

    2015-04-01

    The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double-positive cells from lung, liver, and spleen in healthy mice using seven-color flow cytometry. We identified unique, site-specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC-II. Furthermore, we observed the two known CD45-positive populations (CD45(high) and CD45(int) ) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45(high) population. CD11c-positive microglia lacked MHC-II expression and CD45(high) /CD11c-positive cells from the brain have a lower percentage of MHC-II-positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC-II-positive splenocytes is paralleled by down-regulation of MHC-II, whereas brain-derived mononuclear cells neither ramified nor up-regulated MHC-II in OSSCs. Thus, brain-derived mononuclear cells maintain their MHC-II-negative phenotype within the environment of an immune organ. Intraparenchymal CD11c-positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC-II expression. © 2014 Wiley Periodicals, Inc.

  17. Dynamic changes of Foxp3(+) regulatory T cells in spleen and brain of canine distemper virus-infected dogs.

    Science.gov (United States)

    Qeska, V; Barthel, Y; Iseringhausen, M; Tipold, A; Stein, V M; Khan, M A; Baumgärtner, W; Beineke, A

    2013-12-15

    Canine distemper virus (CDV) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. In viral diseases, an ambiguous function of regulatory T cells (Treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. However, the role of Treg in the pathogenesis of canine distemper remains unknown. In order to determine the effect of CDV upon immune homeostasis, the amount of Foxp3(+) Treg in spleen and brain of naturally infected dogs has been determined by immunohistochemistry. In addition, splenic cytokine expression has been quantified by reverse transcriptase polymerase chain reaction. Splenic depletion of Foxp3(+) Treg was associated with an increased mRNA-expression of tumor necrosis factor and decreased transcription of interleukin-2 in the acute disease phase, indicative of disturbed immunological counter regulation in peripheral lymphoid organs. In the brain, a lack of Foxp3(+) Treg in predemyelinating and early demyelinating lesions and significantly increased infiltrations of Foxp3(+) Treg in chronic demyelinating lesions were observed. In conclusion, disturbed peripheral and CNS immune regulation associated with a reduction of Treg represents a potential prerequisite for excessive neuroinflammation and early lesion development in canine distemper leukoencephalitis. © 2013 Elsevier B.V. All rights reserved.

  18. Strain differences in the expression of an H-2K/sup k/ gene product by epidermal and spleen cells

    International Nuclear Information System (INIS)

    Hadley, G.A.; Steinmuller, D.

    1986-01-01

    Cytotoxic T lymphocytes (CTL) directed against Epa-1, a non-H-2 alloantigen expressed by epidermal cells (EC) but no lymphoid cells, lyse EC of different H-2/sup k/, Epa-1 + strains at different levels. For example, the mean percent lysis values for EC of strains CBA, AKR, C58, and RF are 60, 46, 41, and 35 respectively. Since the CTL used to obtain these values recognize Epa-1 only in the context of H-2K/sup k/, the different levels of lysis could reflect differences in either Epa-1 or K/sup k/ antigens. The goal of this investigation was to test the second alternative. For this purpose, the authors obtained hybridoma 16-1-11N that secretes a K/sup k/-specific MoAb. They first demonstrated the capacity of MoAb 16-1-11N to block the lysis of CBA EC by Epa-1-specific CTL. They then utilized it as the probe in a cellar RIA, with 125 I-protein A as the second reagent, to quantitate the expression of K/sup k/ antigens on EC of strains CBA, AKR, C58, and RF. They found that C58 and RF EC bound significantly less of the K/sup k/ MoAb than CBA EC. Although AKR EC also bound less of the MoAb than CBA EC, the difference was not significant. Nonetheless, these data support the hypothesis that the differential susceptibility of the strains to lysis by Epa-1-specific CTL is due to differences in the expression of the H-2 restricting element. The authors also tested spleen cells (SC) of the four strains in the RIA described above and found that SC of RF, but not of C58 or AKR, express reduced levels of K/sup k/ antigens compared to CBA SC

  19. Toxoplasma gondii vs ionizing radiation: cell and humoral immunity in spleen and gut of isogenic mice immunized with 60Co irradiated tachyzoites

    International Nuclear Information System (INIS)

    Galisteo Junior, Andres Jimenez

    2008-01-01

    We are developing a vaccine for toxoplasmosis, using ionizing radiation as a tool. Here we analyzed the production of systemic and intestinal immunity, with protection studies, in several strains of inbred mice, by oral or parenteral route, using 255 Gy irradiated tachyzoites of T. gondii RH strain, with challenge with cysts of ME- 49 strain. C57Bl/6j, BALB/c and C57Bl/6j IFN-γ -/- mice were immunized with 10 7 irradiated tachyzoites, be parenteral or oral route. Those preparations, both by parenteral or oral routes, induced the production of specific IgG, mainly of the lgG2b subclass, and IgA immunoglobulins in serum, , as determined by ELISA. IgM production was negligible. Parenteral immunized mice showed higher IgG avidity maturation, as compared to oral immunized mice. Fecal excretion of IgG, IgA and IgM was detected in stools of immunized animals, more intense in oral immunized mice. In cellular immunity studies, induced by antigen, with detection of cytokine production by quantitative real-time PCR, there are a great production of IFN-y by spleen cells, with lower levels in Peyer patches cells, where there are a greater IL-2 production. Challenge studies in immunized mice demonstrated protection to infection in all used schedules, greater in BALB/c mice. C57Bl/6j IFN-γ - /- mice, when immunized, showed no signs of disease and produced similar or greater levels of antibodies than wild type mice. They also excreted S-lgA and S-IgM in stools, but with low numbers of brain cysts in parenteral immunized mice, despite similar mortality. Our data points to a fair possibility of use of those irradiated parasites as an oral vaccine, devised to use for veterinary or wild felines vaccination, reducing the production of oocysts by those hosts and interrupting the chain transmission of human toxoplasmosis. (author)

  20. [Morpho-functional reaction of spleen natural killer cells and macrophages to melatonin administration to the animals kept on different illumination regimens].

    Science.gov (United States)

    Shatskikh, O A; Luzikova, E M

    2012-01-01

    The aim this investigation was to study the changes in the numbers of spleen CD57+ and CD68+ cells (natural killer cells and macrophages respectively) after melatonin administration to the animals kept on different illumination regimens. The experimental animals were given melatonin in dose of 0.03 mg per day for 2 and 4 weeks under conditions of natural illumination or artificial darkening. Spleen paraffin sections were stained using immunohistochemical methods for detection of CD57+ and CD68+ cells. It was shown that long-term administration of melatonin under conditions of natural illumination had an immunosuppressive effect, that was manifested by the depopulation of the marginal zones, white pulp and all the zones of the red pulp, parenchyma loosening and denudation of the reticular stroma of the organ. However, long-term hormone administration under conditions of artificial darkening had an immunostimulatory effect as evidenced by the increased inflow of immunocompetent cells into the spleen, their migration from the white pulp into the marginal zones and emigration into peripheral blood flow, concomitant with the increase in the number of lymphoid nodules. The number of CD57+ and CD68+ cells was increased in splenic periarterial lymphoid sheaths and decreased in B-dependent zones of the organ.

  1. Neonatal microbial colonization in mice promotes prolonged dominance of CD11b+Gr-1+cells and accelerated establishment of the CD4+T cell population in the spleen

    DEFF Research Database (Denmark)

    Kristensen, Matilde Bylov; Metzdorff, Stine Broeng; Bergström, Anders

    2015-01-01

    To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b+Gr-1+ splenocytes present perinatally was sustained for a longer period in conventionally...... event, which we suggest impacts the subsequent development of the T cell population in the murine spleen....

  2. In vivo stem cell function of interleukin-3-induced blast cells

    International Nuclear Information System (INIS)

    Tsunoda, J.; Okada, S.; Suda, J.; Nagayoshi, K.; Nakauchi, H.; Hatake, K.; Miura, Y.; Suda, T.

    1991-01-01

    The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, the authors obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells but also into lymphoid lineage cells. The phenotypes of interleukin-3 (IL-3) induced blast colony cells were Thy-1-positive and lineage-marker-negative. They examined whether these blast colony cells contained primitive hematopoietic stem cells in vivo and could reconstitute hematopoietic tissues in lethally irradiated mice. Blast colony cells could generate macroscopic visible spleen colonies on days 8 and 12, and 5 x 10(3) blast cells were sufficient to protect them from lethally irradiation. It was shown that 6 or 8 weeks after transplantation of 5 x 10(3) blast cells, donor male cells were detected in the spleen and thymus of the female recipients but not in the bone marrow by Southern blot analysis using Y-encoded DNA probe. After 10 weeks, bone marrow cells were partially repopulated from donor cells. In a congenic mouse system, donor-derived cells (Ly5.2) were detected in the thymus and spleen 6 weeks after transplantation. Fluorescence-activated cell sorter analyses showed that B cells and macrophages developed from donor cells in the spleen. In the thymus, donor-derived cells were found in CD4, CD8 double-positive, single-positive, and double-negative populations. Reconstitution of bone marrow was delayed and myeloid and lymphoid cells were detected 10 weeks after transplantation. These results indicate that IL-3-induced blast cells contain the primitive hematopoietic stem cells capable of reconstituting hematopoietic organs in lethally irradiated mice

  3. Detection of immunoglobulins containing plasma cells in the thymus, bursa of Fabricius and spleen of vaccinated broiler chickens with Newcastle disease virus vaccine

    Directory of Open Access Journals (Sweden)

    Md. Abdul Masum

    2014-12-01

    Full Text Available Mobilization of immunoglobulins (Igs-containing plasma cells (IgA, IgG and IgM in the spleen, bursa of Fabricius and thymus was investigated in broiler chickens that were vaccinated with Newcastle disease virus (NDV vaccine. In the thymus, the Igs-containing plasma cells were distributed in the cortex and medulla. Their frequency and distribution were higher at D14 and at D28. The number of IgG- and IgM-positive cells was greater than IgA-positive cells in thymus. In the bursa of Fabricius, Igs-containing plasma cells were distributed beneath the capsules; within and around the bursal follicles. Their frequency of occurrence significantly peaked at D14 and at D28 in comparison to day-old chickens, and IgG-positive cells were significantly greater than the IgA- and IgM-positive cells in the bursa of vaccinated chickens. In the spleen, Igs-containing plasma cells were distributed in the white pulp, around the trabeculae, and in the periarterial lymphatic sheath. In this secondary lymphatic tissue, IgG- and IgM-positive cell numbers significantly greater than IgA-positive cells. In conclusion, mobilization of more Igs-positive cells in lymphoid tissues of broiler chickens is due to the effect of NDV vaccine as well as the advancement of age.

  4. Tie2 Expressing Monocytes in the Spleen of Patients with Primary Myelofibrosis.

    Directory of Open Access Journals (Sweden)

    Rita Campanelli

    Full Text Available Primary myelofibrosis (PMF is a Philadelphia-negative (Ph- myeloproliferative disorder, showing abnormal CD34+ progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2 have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs, and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14+ cells are Tie2+ and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2+CD14lowCD16brightCDL62-CCR2- (TEMs and their frequency was higher (p = 0.008 in spleen tissue-derived mononuclear cells (MNCs of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14+ cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14+Tie2+ cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2+ monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ.

  5. The retrorenal spleen

    International Nuclear Information System (INIS)

    Hopper, K.D.; Chantelois, A.E.

    1987-01-01

    An uncommon but potentially disastrous situation for invasive percutaneous renal procedures is the placement of the spleen behind the upper left renal pole. The authors termed this unique anatomic variant ''retrorenal spleen.'' Recently the authors reviewed the CT studies of 85 patients 16-85 years of age scanned in both the supine and prone positions. The relationship of the left kidney and spleen was evaluated. The overall frequency of retrorenal spleen was 12.7% for the supine and 17.9% for the prone studies. Careful correlation was made between the supine and prone studies with respect to the changing anatomic relationship of the kidney and spleen. In addition, the position of the suprarenal spleen was also evaluated in an effort to determine the safety of the subcostal approach

  6. Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN.

    Science.gov (United States)

    Montoya, Maria; Edwards, Matthew J; Reid, Delyth M; Borrow, Persephone

    2005-02-15

    In this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sDC) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (LCMV). Within 24 h postinfection (pi), sDCs acquired the ability to stimulate naive LCMV-specific CD8+ T cells ex vivo. Conventional (CD11chigh CD8+ and CD4+) sDC subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. Their tendency to undergo apoptosis ex vivo simultaneously increased, and in vivo the number of conventional DCs in the spleen decreased markedly, dropping approximately 2-fold by day 3 pi. Conversely, the number of plasmacytoid (CD11clowB220+) DCs in the spleen increased, so that they constituted almost 40% of sDCs by day 3 pi. Type 1 IFN production was up-regulated in plasmacytoid DCs by 24 h pi. Analysis of DC activation and maturation in mice unable to respond to type 1 IFNs implicated these cytokines in driving infection-associated phenotypic activation of conventional DCs and their enhanced tendency to undergo apoptosis, but also indicated the existence of type 1 IFN-independent pathways for the functional maturation of DCs during LCMV infection.

  7. Influence of x-rays and UV-light on the presence of oncogene proteins in spleen cells of leukemic mice

    International Nuclear Information System (INIS)

    Popovic Hadzija, M.; Poljak Blazi, M.

    1996-01-01

    Proto-oncogenes are involved in growth, defferentiation and proliferation of normal cells, and in process of neoplastic transformation. In genome of normal cells, exist also tumor-suppressor genes, which contribute to cancer when they are inactivated. Those genes are target for carcinogenesis provoked by radiation. However, species specific genetic factors are important in determing which, if any, gene will be transformed by radiation. It is possible to presume that oncogenes are involved in the development of radioresistant phenotype of ML. Because of that, we examined the presence of c-myc protein in ML cells during the growth of ML and after the irradiation of these cells. Also, we examined the presence of tumor-suppressor protein p53, because inactivation or loss of p53 gene is in connection with transformation of cells. ML is strain specific for RFM mice. Spleen cells were tested 9 (nonterminal phase NTP) or 12 days (terminal phase TP) after inoculation of ML. Cells from NTP were also irradiate with x-rays or UV-light. C-myc protein expresse 74.98% spleen cells of healthy RFM mice. Wild type of p53 protein was detected in 60% of these cells, but mp53 was found in only 5.3% of cells. These results could be explained by the role of c-myc and p53 proteins in regulation of biologic processes. A few spleen cells of NTP expressed c-myc (15%) and mp53 (9.6%) proteins. But, in the same phase higher expressions of wp53 protein (30.5%) was found. On the other hand, the number of c-myc positive cells in TP of leukemia explanation lies in connection of c-myc protein and process of programmed cell death (apoptosis). During growth of ML the number of mp53 positive cells increased (to 47.8%), but wp53 positive cells decreased (to13.4%9). Both types of irradiation provoked strong activation of cellular c-myc gene in ML cells of NTP. We found about 95% c-myc positive cells after x-rays and 93% after UV-light

  8. Hypersensitive responses of cells in the thymus, spleen, and intestinal crypt of mice to interphase death after treatment with x rays and chemical mutagens

    International Nuclear Information System (INIS)

    Kinuta, Masakatsu

    1986-01-01

    Upon whole-body exposure of mice to X rays or administration of chemical mutagens, cells in thymus, spleen and intestinal crypt undergo sensitive response to interphase death. We developed an effective method for detecting dead cells in the interphase by scoring stained cells in situ in exposed tissues after staining frozen section with erythrosin B. Cell killing was detected at doses as low as 1 % of lethal doses after treatment with X rays and chemicals. Strain N4 was highly sensitive to interphase-cell-death and hybrids of N4 and resistant strain HT or C3H were also sensitive to cell-death, indicating a dominant trait of the sensitive cell-death response. (author)

  9. Effect of peritoneal cavity lavage with 0.9% and 3.0% saline solution in the lung and spleen of gerbils with induced peritonitis.

    Science.gov (United States)

    Nunes, Vinícius Rodrigues Taranto; Barbuto, Rafael Calvão; Vidigal, Paula Vieira Teixeira; Pena, Guilherme Nogueira; Rocha, Silvia Lunardi; de Siqueira, Lucas Tourinho; Caliari, Marcelo Vidigal; de Araujo, Ivana Duval

    2014-04-01

    Peritoneal cavity lavage is used widely in the treatment of peritonitis. Nonetheless, some studies question its rationale and prove it to be deleterious to the mesothelium. The present study aims to determine whether 0.9% and 3.0% saline lavage of the peritoneal cavity have an effect on the early systemic inflammatory response, namely, in the lung injury and splenic cellularity of gerbils with induced peritonitis. Thirty-four male gerbils were divided into four groups: Control (n=9), submitted to laparotomy at time zero, re-laparotomy after 2 h, and sacrificed after a total of 6 h from start; untreated (n=8), submitted to peritonitis induction through cecal ligation and puncture (CLP) at time zero, re-laparotomy intended for drying of abdominal cavity and resection of the ischemic cecum after 2 h, and sacrifice after a total of 6 h from start; saline (n=8), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm 0.9% saline lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start; and hypertonic (n=9), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm hypertonic saline (3.0%) lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start. After sacrifice, we collected the left lung and the spleen for morphometric analysis. In the both the saline and hypertonic groups, there was significant decrease in the mean nuclei count in the lungs, compared with the untreated group (p0.05). The present study demonstrated that the peritoneal lavage with large volumes of warm 0.9% and 3.0% saline has a beneficial effect on the early systemic inflammatory response in infected animals, modulating and reducing the lung injury but having no effect on splenic cell count.

  10. Characterization of the env gene and long terminal repeat of molecularly cloned Friend mink cell focus-inducing virus DNA.

    OpenAIRE

    Adachi, A; Sakai, K; Kitamura, N; Nakanishi, S; Niwa, O; Matsuyama, M; Ishimoto, A

    1984-01-01

    The highly oncogenic erythroleukemia-inducing Friend mink cell focus-inducing (MCF) virus was molecularly cloned in phage lambda gtWES.lambda B, and the DNA sequences of the env gene and the long terminal repeat were determined. The nucleotide sequences of Friend MCF virus and Friend spleen focus-forming virus were quite homologous, supporting the hypothesis that Friend spleen focus-forming virus might be generated via Friend MCF virus from an ecotropic Friend virus mainly by some deletions. ...

  11. Splenocyte proliferation, NK cell activation and cytokines production by extract of Scrophularia variegata; an in vitro study on mice spleen cells

    Directory of Open Access Journals (Sweden)

    A. Azadmehr

    2016-10-01

    Full Text Available Background and objectives:Scrophularia variegata M. Beib. (Scrophulariaceae is a medicinal plant, used for various inflammatory diseases in Iranian Traditional Medicine. In the present study, we evaluated the immune modulation and antioxidant effects of the hydroalcoholic extract of S.  variegata. Methods: The splenocytes were harvested from the spleen of Balb/c mice and were cultured. The splenocyte proliferation, NK cell activity, cytokines production and antioxidant effects were evaluated by MTT assay, enzyme- linked immunosorbent assay (ELISA and DPPH assay, respectively. Results: The S. variegata extract significantly increased splenocyte proliferation. The results indicated that the extract increased NK cell cytotoxicity of Yac-1 tumor cells and at the concentration of 50-200 µg/mL significantly increased IFN-γ and IL-2 cytokines, although the level of IL-4 cytokine was significantly reduced. The antioxidant activity was observed in the extract with IC50 302.34±0.11 μg/mL.Conclusion: The increasing in the splenocyte proliferation, anti-tumor NK cell cytotoxicity and cytokine secretion were indicated as potent immunomodulatory effects. These results suggest that S. variegata could be considered in the treatment of immunopathological disorders such as allergy and cancer; however, future studies are necessary.

  12. Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen

    International Nuclear Information System (INIS)

    Demenesku, Jelena; Mirkov, Ivana; Ninkov, Marina; Popov Aleksandrov, Aleksandra; Zolotarevski, Lidija; Kataranovski, Dragan; Kataranovski, Milena

    2014-01-01

    Highlights: • The effect of cadmium on splenic T and innate immune cells in rats is explored. • Differential effects of 1 mg/kg on T cell and innate immune activities were shown. • Lower Cd dose (0.5 mg/kg) cause less pronounced immunosuppressive effects. • Proinflammatory effects on innate immune activities were seen at that dose. • Presented data depict complexity of immunomodulatory potential of this metal. - Abstract: Conflicting data (both suppression and augmentation as well as lack of the effect) exist in respect to cadmium (Cd) and splenic T cell-based immune cell activity. Spleen is also the site of innate immune responses but impact of Cd on this type of immunity has been less explored. In the present study the effects of acute Cd administration on basic aspects of both T cell-based and innate immune spleen cell activity were examined in rats. Intraperitoneal injection of 1 mg of Cd/kg resulted in decrease in concanavalin A (ConA) induced proliferation which seems to be more related to altered spleen cells responsiveness to IL-2 than to apoptosis. Differential effects on proinflammatory T cell derived cytokines were observed (decreases of IFN-γ gene expression and ConA-stimulated production, but increases in IL-17 mRNA levels with no effect on concentrations of protein product). Reduction of IFN-γ production seemed not to rely on IL-4 and IL-10, but at least partly on nitric oxide (NO). Increased activity relevant for innate immunity (granulocyte and CD11b + cell accumulation in the spleen, inducible nitric oxide synthase/iNOS expression and NO production by spleen cells) was observed, but there was a decrease in respiratory burst (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT reduction). Increases of TNF-α and IL-1β gene expression and IL-1β protein product were noted as well. Administration of 0.5 mg Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack of the effect (IFN-γ production) on spleen T cell

  13. Effects of components of nucleic acid and extracts of the spleen on radiation-induced changes in the permeability of the capillaries. Studies on mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Jaenicke, A

    1973-01-01

    Nucleic acids, their components, and Prosplen, an extract of the spleen, were tested in a radiation experiment. The criterion investigated was the sensitivity of radiation-induced changes in the permeability of the capillaries to parenteral drug administration. For a quantitative assessment, Evans blue was used as a colouring matter. In the late X-ray edema, Laevadosin was the only substance with a significant protective action. In the case of measurements immediately after uv exposure, prophylactic and curative RNA injections have a significant effect even after a filtering-out of a large portion of the spectral part absorbed by DNA and nucleobases. A more than average protective effect is found after a curative intravenous injection of Prosplen. In the case of late measurements following unfiltered uv irradiation, a significant depression of the edema was found for all substances tested.

  14. In vivo immunotoxicity of perfluorooctane sulfonate in BALB/c mice: Identification of T-cell receptor and calcium-mediated signaling pathway disruption through gene expression profiling of the spleen.

    Science.gov (United States)

    Lv, Qi-Yan; Wan, Bin; Guo, Liang-Hong; Yang, Yu; Ren, Xiao-Min; Zhang, Hui

    2015-10-05

    Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that is used worldwide and is continuously being detected in biota and the environment, thus presenting potential threats to the ecosystem and human health. Although PFOS is highly immunotoxic, its underlying molecular mechanisms remain largely unknown. The present study examined PFOS-induced immunotoxicity in the mouse spleen and explored its underlying mechanisms by gene expression profiling. Oral exposure of male BALB/c mice for three weeks followed by one-week recovery showed that a 10 mg/kg/day PFOS exposure damaged the splenic architecture, inhibited T-cell proliferation in response to mitogen, and increased the percentages of T helper (CD3(+)CD4(+)) and cytotoxic T (CD3(+)CD8(+)) cells, despite the decrease in the absolute number of these cells. A delayed type of PFOS immunotoxicity was observed, which mainly occurred during the recovery period. Global gene expression profiling of mouse spleens and QRT-PCR analyses suggest that PFOS inhibited the expression of genes involved in cell cycle regulation and NRF2-mediated oxidative stress response, and upregulated those in TCR signaling, calcium signaling, and p38/MAPK signaling pathways. Western blot analysis confirmed that the expressions of CAMK4, THEMIS, and CD3G, which were involved in the upregulated pathways, were induced upon PFOS exposure. Acute PFOS exposure modulated calcium homoeostasis in splenocytes. These results indicate that PFOS exposure can activate TCR signaling and calcium ion influx, which provides a clue for the potential mechanism of PFOS immunotoxicity. The altered signaling pathways by PFOS treatment as revealed in the present study might facilitate in better understanding PFOS immunotoxicity and explain the association between immune disease and PFOS exposure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Computerized spleen volumetry

    International Nuclear Information System (INIS)

    Jahnke, T.; Mohring, R.; Schertel, L.

    1981-01-01

    We examined in experimental studies and clinical investigations on 34 patients in how far volumetry of the spleen can be carried out with a commonly available program, a whole-body computerized tomograph (SOMATOM) and an analytic equipment (EVALUSKOP). In this connection the authors tried to find also other ways of spleen volumetry by means of this unit combination. Our final result was that the given program for the usage of labelled areas presents itself as the best-suited technique for spleen volumetry which is also applicable in practice. (orig./MG) [de

  16. Overview of the Spleen

    Science.gov (United States)

    ... Neisseria meningitidis , and Haemophilus influenzae . Because of this risk, people receive vaccinations to help protect them from infection with these organisms. People should also be sure they receive the influenza vaccine every year, as is now ... the Spleen ...

  17. Laparoscopic Spleen Removal (Splenectomy)

    Science.gov (United States)

    ... Affairs and Humanitarian Efforts Login Laparoscopic Spleen Removal (Splenectomy) Patient Information from SAGES Download PDF Find a ... are suspected. What are the Advantages of Laparoscopic Splenectomy? Individual results may vary depending on your overall ...

  18. The study of hemopoietic cells. Effect of prolonged irradiation by low dose rate radiation on the hemopoiesis in the spleen of mice

    Energy Technology Data Exchange (ETDEWEB)

    Shirata, Katsutoshi; Yanai, Takanori; Yamada, Yutaka; Saitou, Mikio; Izumi, Jun; Tanaka, Satoshi; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Dept. of Radiobiology, Rokkasho, Aomori (Japan)

    2001-07-01

    For evaluation of effects of prolonged irradiation by low dose-rate ionizing radiation on the hemopoiesis of mice, SPF C3H/HeN female mice were irradiated with {sup 137}Cs {gamma}-rays with doses of 5-8 Gy at the dose rate of 20 mGy/22h-day. After irradiation, the number of hemopoietic cells contained in spleen was determined by the methods of CFU-S and CFU-GM assays, and the number of peripheral blood cells was counted. It was shown that the number of hemopoietic cells (CFU-S colonies and CFU-GM colonies) decreased as dose increased. No remarkable changes in the number of peripheral blood cells, however, were observed. (author)

  19. Mechanisms of tolerance in murine radiation bone marrow chimeras. I. Nonspecific suppression of alloreactivity by spleen cells from early, but not late, chimeras

    International Nuclear Information System (INIS)

    Auchincloss, H. Jr.; Sachs, D.H.

    1983-01-01

    Allogeneic chimeras were prepared using lethally irradiated B6 hosts and untreated marrow from exsanguinated BALB/c donors. For about two months after reconstitution, chimeras had very weak antihost cell-mediated lymphocytotoxicity (CML) reactivity and little third-party alloreactivity. During this time a cell population capable of suppressing CML reactivity against both host and third-party alloantigens (i.e., antigen-nonspecific) was demonstrated in chimera spleens by in vitro mixing experiments. The putative suppressor cells were Thy-1-negative and radiation-sensitive. Subsequently, mature chimeras showed host tolerance and strong third-party alloreactivity. At this point suppressor mechanisms could no longer be demonstrated. These data are consistent with a clonal elimination hypothesis in that they do not provide evidence to indicate that maintenance of specific immune tolerance is mediated by an active suppressor mechanism

  20. Investigations of the radiosensitivity of enzymes of the NAD metabolism localized in the cell nucleus in the spleen of white mice

    International Nuclear Information System (INIS)

    Beisel, P.

    1975-01-01

    The radiosensitivity of enzymes of the NAD metabolism localized in the cell nuclei and of NAD glycohydrolase in the total homogenate of the spleen of white mice was investigated. At the same time the DNA and protein contents were determined. After whole-body irradiation with 510 R, the activity of NAD pyrophosphorylase and NAD glycohydrolase located in the cell nuclei is markedly lower as early as 3 hours after irradiation; this decrease is noticeable until the 10th day after irradiation. With regard to the dose dependence of the radiosensitivity at 6 and 24 hours after irradiation, it was found that NAD pyrophosphorylase and the NAD glycohydrolase localized in the cell nuclei were very radiosensitive even at doses [de

  1. Anti-double strand (ds) DNA antibody formation by NZB/W (F1) spleen cells in a microculture system detected by solid phase radioimmunoassay.

    Science.gov (United States)

    Okudaira, H; Terada, E; Ogita, T; Aotsuka, S; Yokohari, R

    1981-01-01

    A solid-phase radioimmunoassay method was devised to detect mouse anti-double strand (ds) DNA antibody. This method could easily detect the anti-dsDNA antibody in 1 : 10,000 dilutions (1 unit) of pooled 9-10-month-old female NZB/W F1 sera. The sensitivity was about 10(3)- and 10(2)-fold higher than that of the modified Farr method and of the double antibody technique respectively. NZB/W mice developed high titer anti-dsDNA antibody as they grew older. Spleen cells brought to a microculture system using flat-bottomed polystyrene plates produced anti-dsDNA antibody clearly detectable by solid-phase radioimmunoassay. Anti-dsDNA antibody produced in vitro (y units) was in close correlation with the anti-dsDNA antibody titer of the spleen donor (x units) (y = 4.8 X 10(-2) x -65, gamma = 0.94, P less than 0.001). A combination of the microculture system and solid-phase radioimmunoassay was recommended for the characterization of anti-dsDNA antibody-forming cells.

  2. Anti-double strand (ds) DNA antibody formation by NZB/W (F1) spleen cells in a microculture system detected by solid-phase radioimmunoassay

    International Nuclear Information System (INIS)

    Okudaira, H.; Terada, E.; Ogita, T.; Aotsuka, S.; Yokohari, R.

    1981-01-01

    A solid-phase radioimmunoassay method was devised to detect mouse anti-double strand (ds) DNA antibody. This method could easily detect the anti-ds DNA antibody in 1 : 10,000 dilutions (1 unit) of pooled 9-10 month-old female NZB/W F1 sera. The sensitivity was about 10 3 and 10 2 -fold higher than that of the modified Farr method and of the double antibody technique respectively. NZB/W mice developed high titer anti-dsDNA antibody as they grew older. Spleen cells brought to a microculture system using flat-bottomed polystyrene plates produced anti-dsDNA antibody clearly detectable by solid-phase radioimmunoassay. Anti-dsDNA antibody produced in vitro (y units) was in close correlation with the anti-dsDNA antibody titer of the spleen donor (x units) (y = 4.8 X 10 -2 x-65, γ = 0.94, P < 0.001). A combination of the microculture system and solid-phase radioimmunoassay was recommended for the characterization of anti-dsDNA antibody-forming cells. (Auth.)

  3. Scintigraphic diagnosis and computed tomographic localization of an accessory spleen following relapse of chronic immune thrombocytopaenia

    International Nuclear Information System (INIS)

    Cardaci, G.T.; Blake, M.P.

    1992-01-01

    Chronic immune thrombocytopaenia is an immunologically mediated disorder resulting in disordered platelet kinetics and potentially life-threatening disease. Failure of medical therapy is an indication for splenectomy, and responses are seen in 80% of patients following this procedure. An important cause of relapse following splenectomy is the presence of an accessory spleen. A patient with Hodgkin's Disease developed chronic immune thrombocytopaenia despite previous splenectomy. A remission was induced with immunosuppressive therapy, but he later relapsed. An accessory spleen was detected using 99 m Tc denatured red blood cells and localized using computed tomography. Resection of the accessory spleen resulted in clinical remission. As accessory spleens are often small in size, combined modality imaging is recommended in the evaluation of this disorder. 15 refs., 2 figs

  4. Changes in protein metabolism after irradiation. Pt. 1. Protease activity, protease pattern, protein and free amino acids in cytoplasm and cell organelles of the rat spleen after 600 R whole body x irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Valet, G [Max-Planck-Institut fuer Biochemie, Muenchen (F.R. Germany). Abt. fuer Experimentelle Medizin

    1975-12-01

    The protease activity of cytoplasm and cell organelles of the rat spleen against spleen protein and hemoglobin as a substrate increases during a initial reaction phase of the organism on the first day after 600 R whole body X-irradiation. The alkaline protease in the cytoplasm and the acid protease in the cell organelles increase, whereas the protease activity against externally added hemoglobin as substrate decreases below the initial values. The protein, the protease activity and the free amino acids of the cytoplasm and the cell organelles decrease during the disease phase on day 3 and 4 after irradiation. The protein loss of the spleen is therefore not explained by an increased protease activity. Acid proteases appear in the cytoplasm which derive probably from the cell organelles. The protease activity and the free amino acids are increased in the cytoplasm and the cell organelles during the regeneration phase of the organism between day 15 and 18 after irradiation.

  5. Partial spleen embolization reduces the risk of portal hypertension-induced upper gastrointestinal bleeding in patients not eligible for TIPS implantation.

    Science.gov (United States)

    Buechter, Matthias; Kahraman, Alisan; Manka, Paul; Gerken, Guido; Dechêne, Alexander; Canbay, Ali; Wetter, Axel; Umutlu, Lale; Theysohn, Jens M

    2017-01-01

    Upper gastrointestinal bleeding (UGIB) is a severe and life-threatening complication among patients with portal hypertension (PH). Covered transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for patients with refractory or recurrent UGIB despite pharmacological and endoscopic therapy. In some patients, TIPS implantation is not possible due to co-morbidity or vascular disorders. Spleen embolization (SE) may be a promising alternative in this setting. We retrospectively analyzed 9 patients with PH-induced UGIB who underwent partial SE between 2012 and 2016. All patients met the following criteria: (i) upper gastrointestinal hemorrhage with primary or secondary failure of endoscopic interventions and (ii) TIPS implantation not possible. Each patient was followed for at least 6 months after embolization. Five patients (56%) suffered from cirrhotic PH, 4 patients (44%) from non-cirrhotic PH. UGIB occured in terms of refractory hemorrhage from gastric varices (3/9; 33%), hemorrhage from esophageal varices (3/9; 33%), and finally, hemorrhage from portal-hypertensive gastropathy (3/9; 33%). None of the patients treated with partial SE experienced re-bleeding episodes or required blood transfusions during a total follow-up time of 159 months, including both patients with cirrhotic- and non-cirrhotic PH. Partial SE, as a minimally invasive intervention with low procedure-associated complications, may be a valuable alternative for patients with recurrent PH-induced UGIB refractory to standard therapy.

  6. Immortalized porcine mesenchymal cells derived from nasal mucosa, lungs, lymph nodes, spleen and bone marrow retain their stemness properties and trigger the expression of siglec-1 in co-cultured blood monocytic cells.

    Science.gov (United States)

    Garba, Abubakar; Desmarets, Lowiese M B; Acar, Delphine D; Devriendt, Bert; Nauwynck, Hans J

    2017-01-01

    Mesenchymal stromal cells have been isolated from different sources. They are multipotent cells capable of differentiating into many different cell types, including osteocytes, chondrocytes and adipocytes. They possess a therapeutic potential in the management of immune disorders and the repair of damaged tissues. Previous work in our laboratory showed an increase of the percentages of CD172a+, CD14+, CD163+, Siglec-1+, CD4+ and CD8+ hematopoietic cells, when co-cultured with immortalized mesenchymal cells derived from bone marrow. The present work aimed to demonstrate the stemness properties of SV40-immortalized mesenchymal cells derived from nasal mucosa, lungs, spleen, lymph nodes and red bone marrow and their immunomodulatory effect on blood monocytes. Mesenchymal cells from nasal mucosa, lungs, spleen, lymph nodes and red bone marrow were isolated and successfully immortalized using simian virus 40 large T antigen (SV40LT) and later, co-cultured with blood monocytes, in order to examine their differentiation stage (expression of Siglec-1). Flow cytometric analysis revealed that the five mesenchymal cell lines were positive for mesenchymal cell markers CD105, CD44, CD90 and CD29, but lacked the expression of myeloid cell markers CD16 and CD11b. Growth analysis of the cells demonstrated that bone marrow derived-mesenchymal cells proliferated faster compared with those derived from the other tissues. All five mesenchymal cell lines co-cultured with blood monocytes for 1, 2 and 7 days triggered the expression of siglec-1 in the monocytes. In contrast, no siglec-1+ cells were observed in monocyte cultures without mesenchymal cell lines. Mesenchymal cells isolated from nasal mucosa, lungs, spleen, lymph nodes and bone marrow were successfully immortalized and these cell lines retained their stemness properties and displayed immunomodulatory effects on blood monocytes.

  7. Borrelia-induced cytokine production is mediated by spleen tyrosine kinase (Syk) but is Dectin-1 and Dectin-2 independent

    NARCIS (Netherlands)

    Oosting, M.; Buffen, K.; Cheng, S.C.; Verschueren, I.C.; Koentgen, F.; Veerdonk, F.L. van de; Netea, M.G.; Joosten, L.A.B.

    2015-01-01

    Although it is known that Borrelia species express sugar-like structures on their outer surface, not much is known about the role of these structures in immune recognition by host cells. Fungi, like Candida albicans, are mainly recognized by C-type lectin receptors, in specific Dectin-1 and

  8. Follicular dendritic cell-specific prion protein (PrP expression alone is sufficient to sustain prion infection in the spleen.

    Directory of Open Access Journals (Sweden)

    Laura McCulloch

    2011-12-01

    Full Text Available Prion diseases are characterised by the accumulation of PrP(Sc, an abnormally folded isoform of the cellular prion protein (PrP(C, in affected tissues. Following peripheral exposure high levels of prion-specific PrP(Sc accumulate first upon follicular dendritic cells (FDC in lymphoid tissues before spreading to the CNS. Expression of PrP(C is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrP(C expression was specifically "switched on" or "off" only on FDC. We show that PrP(C-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrP(C-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrP(C expression on FDC.

  9. Liver and spleen scintigraphy

    International Nuclear Information System (INIS)

    Devries, D.F.

    1988-01-01

    Since the introduction of liver and spleen scintigraphy in the early 1950s, it has undergone considerable changes, the most notable being technetium 99m sulfur colloid, the gamma camera, and single photon emission computed tomography (SPECT). What is the role f liver-spleen scintigraphy in this high-technology society? This chapter attempts to address this question by looking at the radiopharmaceuticals, the technique, and most importantly, the application of scintigraphy to the diagnosis of focal and diffuse hepatic and splenic disease

  10. The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cell immigration and T-cell zone formation during ontogeny of the spleen.

    Science.gov (United States)

    Rumfelt, L L; McKinney, E C; Taylor, E; Flajnik, M F

    2002-08-01

    Secondary lymphoid tissue and immunoglobulin (Ig) production in mammals is not fully developed at birth, requiring time postnatally to attain all features required for adaptive immune responses. The immune system of newborn sharks - the oldest vertebrate group having adaptive immunity - also displays immature characteristics such as low serum IgM concentration and high levels of IgM1gj, an innate-like Ig. Primary and secondary lymphoid tissues in sharks and other cartilaginous fish were identified previously, but their cellular organization was not examined in detail. In this study of nurse shark lymphoid tissue, we demonstrate that the adult spleen contains well-defined, highly vascularized white pulp (WP) areas, composed of a central T-cell zone containing a major histocompatibility complex (MHC) class II+ dendritic cell (DC) network and a small number of Ig+ secretory cells, surrounded by smaller zones of surface Ig+ (sIg+) B cells. In neonates, splenic WPs are exclusively B-cell zones containing sIgM+-MHC class IIlow B cells; thus compartmentalized areas with T cells and DCs, as well as surface Ig novel antigen receptor (sIgNAR)-expressing B cells are absent at birth. Not until the pups are 5 months old do these WP areas become adult-like; concomitantly, sIgNAR+ B cells are readily detectable, indicating that this Ig class requires a 'mature immune-responsive environment'. The epigonal organ is the major site of neonatal B lymphopoiesis, based on the presence of developing B cells and recombination-activating gene 1 (RAG1)/terminal deoxynucleotidyl transferase (TdT) expression, indicative of antigen receptor rearrangement; such expression persists into adult life, whereas the spleen has negligible lymphopoietic activity. In adults but not neonates, many secretory B cells reside in the epigonal organ, suggesting, like in mammals, that B cells home to this primary lymphoid tissue after activation in other areas of the body.

  11. Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice.

    Science.gov (United States)

    Suto, J; Wakayama, T; Imamura, K; Goto, S; Fukuta, K

    1995-08-01

    The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

  12. Radiology of the spleen

    International Nuclear Information System (INIS)

    Robertson, F.; Leander, P.; Ekberg, O.

    2001-01-01

    The spleen is generally not considered a challenge to the radiologist. Most often it poses a problem by anomalies or an irregular but normal contrast enhancement; however, a variety of inflammatory, infectious and neoplastic diseases may involve the spleen. CT and ultrasonography are screening modalities for the spleen. For problem solving, MR imaging can be helpful, especially due to its free choice of the imaging plane and because of the high resolution in contrast MR imaging. Splenic angiography as a diagnostic tool has generally been replaced by CT, ultrasound, or MR and is now used as an interventional method, e.g., in non-surgical management of patients with chronic idiopathic thrombocytopenia or in patients with splenic trauma. This article reviews the radiology of the spleen, including anatomy, embryology, splenomegaly, splenic injury, infarction, cysts, tumors, abscesses, sarcoidosis, and AIDS. Knowledge about the use of different imaging modalities and underlying gross and microscopic pathologic features leads to a better understanding of the radiologic findings. (orig.)

  13. {sup 99} {sup m}Tc-sulphur-colloid and heat-denatured {sup 99} {sup m}Tc-labelled red cell scans demonstrating a giant intrapelvic spleen in a girl after splenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Kao, P.F. [Dept. of Nuclear Medicine, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Tauyuan, Taiwan (Taiwan); Dept. of Nuclear Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (Taiwan); Tzen, K.Y.; Tsai, M.F. [Dept. of Nuclear Medicine, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Tauyuan, Taiwan (Taiwan); Lin, J.N. [Dept. of Paediatric Surgery, Chang Gung Childrens Hospital and Chang Gung University School of Medicine, Tauyuan, Taiwan (Taiwan)

    2001-04-01

    A 17 x 12 x 5-cm giant intrapelvic mass in a 14-year-old girl is reported. This mass developed 6 years after a splenectomy for splenic torsion. The heat-denatured {sup 99} {sup m}Tc-labelled red cell scan and {sup 99} {sup m}Tc- sulphur-colloid scan confirmed the specific red cell sequestration function and reticuloendothelial activity in the giant intrapelvic spleen. The size and development of the giant intrapelvic spleen are unusual. The usefulness of functional images to diagnosis the nature of the intrapelvic mass is well demonstrated. (orig.)

  14. CD8+ T cells induce thyroid epithelial cell hyperplasia and fibrosis.

    Science.gov (United States)

    Yu, Shiguang; Fang, Yujiang; Sharav, Tumenjargal; Sharp, Gordon C; Braley-Mullen, Helen

    2011-02-15

    CD8(+) T cells can be important effector cells in autoimmune inflammation, generally because they can damage target cells by cytotoxicity. This study shows that activated CD8(+) T cells induce thyroid epithelial cell hyperplasia and proliferation and fibrosis in IFN-γ(-/-) NOD.H-2h4 SCID mice in the absence of CD4(+) T cells. Because CD8(+) T cells induce proliferation rather than cytotoxicity of target cells, these results describe a novel function for CD8(+) T cells in autoimmune disease. In contrast to the ability of purified CD8(+) T cells to induce thyrocyte proliferation, CD4(+) T cells or CD8 T cell-depleted splenocytes induced only mild thyroid lesions in SCID recipients. T cells in both spleens and thyroids highly produce TNF-α. TNF-α promotes proliferation of thyrocytes in vitro, and anti-TNF-α inhibits development of thyroid epithelial cell hyperplasia and proliferation in SCID recipients of IFN-γ(-/-) splenocytes. This suggests that targeting CD8(+) T cells and/or TNF-α may be effective for treating epithelial cell hyperplasia and fibrosis.

  15. Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.

    Science.gov (United States)

    Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

    2015-11-01

    Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. DX5+NKT cells display phenotypical and functional differences between spleen and liver as well as NK1.1-Balb/c and NK1.1+ C57Bl/6 mice.

    Science.gov (United States)

    Werner, Jens M; Busl, Elisabeth; Farkas, Stefan A; Schlitt, Hans J; Geissler, Edward K; Hornung, Matthias

    2011-04-29

    Natural killer T cells represent a linkage between innate and adaptive immunity. They are a heterogeneous population of specialized T lymphocytes composed of different subsets. DX5+NKT cells are characterized by expression of the NK cell marker DX5 in the context of CD3. However, little is known about the phenotype and functional capacity of this unique cell population. Therefore, we investigated the expression of several T cell and NK cell markers, as well as functional parameters in spleen and liver subsets of DX5+NKT cells in NK1.1- Balb/c mice and compared our findings to NK1.1+ C57Bl/6 mice. In the spleen 34% of DX5+NKT cells expressed CD62L and they up-regulated the functional receptors CD154 as well as CD178 upon activation. In contrast, only a few liver DX5+NKT cells expressed CD62L, and they did not up-regulate CD154 upon activation. A further difference between spleen and liver subsets was observed in cytokine production. Spleen DX5+NKT cells produced more Th1 cytokines including IL-2, IFN-γ and TNF-α, while liver DX5+NKT cells secreted more Th2 cytokines (e.g. IL-4) and even the Th17 cytokine, IL-17a. Furthermore, we found inter-strain differences. In NK1.1+ C57Bl/6 mice DX5+NKT cells represented a distinct T cell population expressing less CD4 and more CD8. Accordingly, these cells showed a CD178 and Th2-type functional capacity upon activation. These results show that DX5+NKT cells are a heterogeneous population, depending on the dedicated organ and mouse strain, that has diverse functional capacity.

  17. Hemangiopericytoma of the spleen.

    Science.gov (United States)

    Illuminati, Giulio; Pizzardi, Giulia; Calio, Francesco; Pacilè, Maria A; Carboni, Fabio; Palumbo, Piergaspare; Vietri, Francesco

    2015-03-01

    Hemangiopericytoma of the spleen is a very rare tumor, with 14 isolated reports. It was our aim to review our experience and compare it with all the reported cases in an attempt to standardize surgical treatment, adjuvant treatment and follow-up protocol of this infrequent condition. A consecutive case series study, with a mean follow-up of 44 months. Five patients (mean age, 49 years) underwent simple splenectomy for hemangiopericytoma limited to the spleen followed by adriamycin-based chemotherapy in one patient. All the patients are alive and free from disease. For tumors confined to the spleen, simple splenectomy can be considered curative, without any need for further adjuvant treatment. On review of the medical literature, cure can still be achieved with complete resection of recurrences, when feasible, with adjuvant chemotherapy being also indicated. The slow-growing pattern of the tumor suggests a 10-year follow-up. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  18. The role of thymus-dependent T cells in hexachlorobenzene-induced inflammatory skin and lung lesions

    NARCIS (Netherlands)

    Michielsen, CCPPC; Bloksma, N; Klatter, FA; Rozing, J; Vos, JG; van Dijk, JE

    1999-01-01

    The involvement of thymus-dependent T cells in the inflammatory skin and lung lesions and spleen effects induced by hexachlorobenzene (HCB) was investigated by using genetically athymic and euthymic WAG/Rij rats and Brown Norway (BN) rats with or without depletion of T cells by adult thymectomy,

  19. Novel technique to measure total IgM and IgG in vitro haemolysin production by mouse spleen cells, using /sup 51/Cr-labelled sheep red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Liske, R [Hoffmann-La Roche (F.) and Co., Basel (Switzerland)

    1980-06-12

    A quantitative method for measuring in vitro production of IgM and IgG haemolysis is described. Immune mouse spleen cells, /sup 51/Cr-labelled sheep red blood cells, guinea pig complement and -where applicable- rabbit anti-mouse gammaglobulin serum are incubated in the fluid phase at 37/sup 0/C, and the degree of chromium release measured in the supernatent. The assay gives reproducible results which compare well with the numbers of plaque-forming cells obtained in the conventional plaque-forming assay.

  20. Paediatric Wandering Spleens in Malawi

    African Journals Online (AJOL)

    by a double layer of peritoneum. The wandering spleen is the rare description of an abnormally positioned spleen, which is thought to occur due to laxity, abnormality or absence of the aforementioned ligaments. The wandering spleen is noted to have a longer than normal pedicle, and because of its intraperitoneal location, ...

  1. Severe T-cell depletion from the PALS leads to altered spleen composition in common marmosets with experimental autoimmune encephalomyelitis (EAE)

    NARCIS (Netherlands)

    De Vos, Alex F; van Riel, Debby A J; van Meurs, Marjan; Brok, Herbert P M; Boon, Louis; Hintzen, Rogier Q; Claassen, Eric H J H M; 't Hart, Bert A; Laman, Jon D

    Recent data suggest that the spleen is a crucial component of the immune system in the development of experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys. Using immunohistochemistry, we investigated changes in the distribution of leukocytes in the spleen associated with clinical

  2. Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

    International Nuclear Information System (INIS)

    Holásková, Ida; Elliott, Meenal; Hanson, Miranda L.; Schafer, Rosana; Barnett, John B.

    2012-01-01

    Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl 2 (10 ppm) and the effects on the immune system of the offspring were assessed at 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4 − CD8 − CD44 + CD25 − (DN1) thymocytes in both sexes and a decrease in the percent of CD4 − CD8 − CD44 − CD25 + (DN3) thymocytes in females. Females had an increase in the percent of splenic CD4 + T cells, CD8 + T cells, and CD45R/B220 + B cells and a decrease in the percent of NK cells and granulocytes (Gr-1 + ). Males had an increase in the percent of splenic CD4 + T cells and CD45R/B220 + B cells and a decrease in the percent of CD8 + T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed. ► Males and females had changed percentages of numerous splenic cell

  3. Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

    Energy Technology Data Exchange (ETDEWEB)

    Holásková, Ida; Elliott, Meenal; Hanson, Miranda L.; Schafer, Rosana [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV 26506 (United States)

    2012-12-01

    Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4{sup −}CD8{sup −}CD44{sup +}CD25{sup −} (DN1) thymocytes in both sexes and a decrease in the percent of CD4{sup −}CD8{sup −}CD44{sup −}CD25{sup +} (DN3) thymocytes in females. Females had an increase in the percent of splenic CD4{sup +} T cells, CD8{sup +} T cells, and CD45R/B220{sup +} B cells and a decrease in the percent of NK cells and granulocytes (Gr-1{sup +}). Males had an increase in the percent of splenic CD4{sup +} T cells and CD45R/B220{sup +} B cells and a decrease in the percent of CD8{sup +} T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed

  4. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-01-01

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57 Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the 57 Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues

  5. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Science.gov (United States)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-04-01

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

  6. The {sup 57}Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@gmail.com; Alenkina, I. V. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation); Vinogradov, A. V.; Konstantinova, T. S. [Ural State Medical University (Russian Federation); Semionkin, V. A. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation)

    2015-04-15

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the {sup 57}Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the {sup 57}Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues.

  7. Characteristics of cells producing stimulator for the proliferation of colony forming unit-spleen (CFU-S)

    International Nuclear Information System (INIS)

    Abdul Manaf Ali; Wright, E.G.; Riches, A.C.

    1994-01-01

    The presence of stimulator for haemopoietic stem cell (CFU-S) proliferation in regenerating bone marrow was assayed by incubating the conditioned medium (CM) prepared from bone marrow with quiescent CFU-S from normal bone marrow. The percentage of CFU-S normal bone marrow in DNA synthesis increased more than 30 percent after incubating with CM of 4.5 Gy regenerating bone marrow. Stimulator was also present in bone marrow of mice at 9.0 Gy whole body X-irradiation. However the conditioned medium prepared from regenerating bone marrow without Fc and Ia-2k cells failed to increase the percentage of CFU-S in DNA synthesis. On the other hand, elimination of Thy 1.2 positive cells with complement cytolysis did not affect the ability of regenerating bone marrow to produce stimulator. These observations suggest that the stimulator producing cells are radio-resistant, Thy 1.2 negative, Fc and Ia-2k positive

  8. Relationship between number of spleen colonies and 125IdUrd incorporation into spleen and femur

    International Nuclear Information System (INIS)

    Inoue, T.; Bullis, J.E.; Cronkite, E.P.; Hubner, G.E.

    1983-01-01

    Graded numbers of bone marrow (BM) cells were injected into fatally irradiated mice. Eight days later the mice were given 3.0 μCi (1 Ci = 3.7 x 10 10 Bq) of 125 IdUrd to label proliferating cells in the spleen and BM. On day 9 the mice were killed and the spleens and femurs were removed for splenic colony assay and measurement of radioactivity in the spleen and femurs. The number of splenic colonies shows a linear relationship with dose of marrow cells injected from 10 4 to 10 5 cells. The slope of the curve of spleen colonies versus number of cells injected is 5 and below 10 4 there is a striking departure from the simple linearity. Below 2 x 10 3 cells injected, the logarithm of the observed colony yield is linear with logarithm of the number of cells injected. Poisson calculation of the average number of pluripotent stem cells that should be present with numbers of marrow cells injected below 2 x 10 3 followed closely the actual observations. The data show that there is no detectible proliferation in the BM until the dose of marrow cells exceeds 3.5 x 10 4 cells. Induction of cells into cycle increases the seeding into the BM, and thymidine cytocide drastically reduces seeding in the BM, leading us to conclude that the BM is repopulated almost exclusively by stem cells in DNA synthesis

  9. Binding of a diphosphorylated-ITAM peptide to spleen tyrosine kinase (Syk) induces distal conformational changes : a hydrogen exchange mass spectrometry study

    NARCIS (Netherlands)

    Catalina, M Isabel; Fischer, Marcel J E; Liskamp, Rob M J; Heck, Albert J R; Dekker, Frank

    Structural flexibility plays a crucial role in protein function. To assess whether specific structural changes are associated with the binding of an immunoreceptor tyrosine-based activation motif (ITAM) to the tandem Src homology-2 domains (tSH2) of the spleen tyrosine kinase [EC 2.7.7.112] (Syk),

  10. Solid solitary hamartoma of the spleen

    Directory of Open Access Journals (Sweden)

    Grubor Nikica

    2013-01-01

    Full Text Available Introduction. Hamartoma of the spleen is a rare, sometimes asymptomatic similar to hemangioma benign tumor of the spleen, which, owing to the new diagnostic imaging methods, is discovered with increasing frequency. It appears as solitary or multiple tumorous lesions. Case Outline. We present a 48-year-old woman in whom, during the investigation for Helicobacter pylori gastric infection and rectal bleeding, with ultrasonography, a mass 6.5×6.5 cm in diameter was discovered by chance within the spleen. Splenectomy was performed due to suspected lymphoma of the spleen. On histology, tumor showed to be of mixed cellular structure, with areas without white pulp, at places with marked dilatation of sinusoids and capillaries to the formation of „blood lakes“ between which broad hypercellular Billroth’s zones were present. Extramedullary hematopoiesis was found focally. The cells that covered vascular spaces were CD34+ and CD31+ and CD8- and CD21-. Conclusion. Hamartoma has to be taken into consideration always when well circumscribed hypervascular tumor within the spleen is found, particularly in children. Although the diagnosis of hamartoma may be suspected preoperatively, the exact diagnosis is established based on histological and immunohystochemistry examinations. Treatment is most often splenectomy and rarely a partial splenectomy is possible, which is recommended particularly in children.

  11. Fetal and adult hematopoietic stem cells require beta1 integrin function for colonizing fetal liver, spleen, and bone marrow

    DEFF Research Database (Denmark)

    Potocnik, A J; Brakebusch, C; Fässler, R

    2000-01-01

    hematolymphoid differentiation potential in vitro and in fetal organ cultures but were unable to seed fetal and adult hematopoietic tissues. Adult beta1 integrin null HSCs isolated from mice carrying loxP-tagged beta1 integrin alleles and ablated for beta1 integrin expression by retroviral cre transduction......Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had...

  12. Dose-rate effects and chronological changes of chromosome aberration rates in spleen cells from mice that are chronically exposed to gamma-ray at low dose rates

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Kohda, Atsushi; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Oghiso, Yoichi

    2006-01-01

    Dose-rate effects have not been examined in the low dose-rate regions of less than 60-600 mGy/h. Mice were chronically exposed to gamma-ray at 20 mGy/day (approximately 1 mGy/h) up to 700 days and at 1 mGy/day (approximately 0.05 mGy/h) for 500 days under SPF conditions. Chronological changes of chromosome aberration rates in spleen cells were observed along with accumulated doses at both low dose-rates. Unstable aberrations increased in a biphasic manner within 0-2 Gy and 4-14 Gy in 20 mGy/day irradiation. They slightly increased up to 0.5 Gy in 1 mGy/day irradiation. Chromosome aberration rates at 20 mGy/day and 1 mGy/day were compared at the same total doses of 0.5 Gy and 0.25 Gy. They were 2.0 vs. 0.53, and 1.0 vs. 0.47 respectively. Thus, dose-rate effects were observed in these low dose-rate regions. (author)

  13. Changes in antigen-presenting cell function in the spleen and lymph nodes of ultraviolet-irradiated mice

    International Nuclear Information System (INIS)

    Gurish, M.F.; Lynch, D.H.; Daynes, R.A.

    1982-01-01

    It has been previously reported that mice exposed to ultraviolet (UV) radiation exhibit a decrease in splenic antigen-presenting cell (APC) function. The results presented here confirm this observation and further demonstrate that animals exposed daily to UV for extended periods of time (5 weeks instead of 6 days) no longer exhibit this depressed capability. In spite of the depression in splenic APC activity found in 6-day UV-irradiated mice, lymph node APC function from these same animals was elevated compared with that found in the lymph nodes from normal animals. Lymph node APC activity in animals that were splenectomized prior to the UV irradiation, however, was not enhanced over controls. Treatment of animals with a chemical irritant (turpentine) also caused a depression in splenic APC function without modifying lymph node activity. Collectively, our findings suggest that the observed decrease in splenic APC activity, found after the first week of UV exposures, may be attributable to the migration of splenic APC to peripheral lymphoid tissue which drain the site of epidermal inflammation

  14. A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes

    NARCIS (Netherlands)

    Cha, Hoon-Suk; Boyle, David L.; Inoue, Tomoyuki; Schoot, Reineke; Tak, Paul P.; Pine, Polly; Firestein, Gary S.

    2006-01-01

    Spleen tyrosine kinase (Syk) is a key regulator of cell signaling induced by cytokines or Fc receptor engagement. However, the role of Syk in rheumatoid arthritis (RA) is not known yet. We investigated the pathways activated by Syk in tumor necrosis factor-alpha (TNFalpha)-stimulated fibroblast-like

  15. Isolated Amoebic Abscess of Spleen

    Directory of Open Access Journals (Sweden)

    Kaushik M

    2013-04-01

    Full Text Available Amoebic liver abscess is the most common extraintestinal manifestation of amoebiasis. Extrahepatic amoebic abscesses have occasionally been described in the lung, brain, and skin and presumably result from hematogenous spread. Isolated amoebic abscess of spleen has been reported scarcely in literature. We report here a case of isolated amoebic abscess of spleen.

  16. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Choi, Hyeong-Jwa [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Na, Tae-Young [College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-741 (Korea, Republic of); Nemeno, Judee Grace E.; Lee, Jeong Ik [Regenerative Medicine Laboratory, Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul, 143-701 (Korea, Republic of); Yoon, Taek Joon [Department of Food and Nutrition, Yuhan College, Bucheon, Gyeonggi-do, 422-749 (Korea, Republic of); Choi, In-Soo [Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Lee, Minyoung [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Lee, Jae-Seon [Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 400-712 (Korea, Republic of); Kang, Young-Sun, E-mail: kangys1967@naver.com [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of)

    2015-08-07

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.

  17. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    International Nuclear Information System (INIS)

    Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee; Choi, Hyeong-Jwa; Na, Tae-Young; Nemeno, Judee Grace E.; Lee, Jeong Ik; Yoon, Taek Joon; Choi, In-Soo; Lee, Minyoung; Lee, Jae-Seon; Kang, Young-Sun

    2015-01-01

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3 + apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b + cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1 + macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver

  18. Homeopathic medicines cause Th1 predominance and induce spleen and megakaryocytes changes in BALB/c mice infected with Leishmania infantum.

    Science.gov (United States)

    Cajueiro, Ana Paula Bacellar; Goma, Ester Puna; Dos Santos, Hilton Antônio Mata; Almeida Rodrigues, Igor; Toma, Helena Keiko; Araújo, Silvana Marques; Bonamin, Leoni Villano; Gomes, Nelson Brêtas de Noronha; Castelo-Branco, Morgana Teixeira Lima; de Souza Dias, Edilma Paraguai; Dos Santos Pyrrho, Alexandre; Holandino, Carla

    2017-07-01

    The prevalence of Th1/Th2 response, spleen changes and megakaryocytes were investigated in BALB/c mice (n=138) infected with Leishmania infantum, and treated with Leishmania infantum 30× (10 -30 ) biotherapy - BioLi30×. We performed controlled experiments using 8-to-12-week-old mice, infected with 5×10 7 L. infantum promastigotes, divided into eight groups: G1 (healthy), G2 (infected with L. infantum), G3 (BioLi30× pre-treated), G4 (BioLi30× pre/post-treated), G5 (BioLi30× post-treated), G6 (Water 30× post-treated), G7 (Antimonium crudum 30× post-treated) and G8 (Glucantime® post-treated). G3-G7 groups were orally treated with their respective drugs diluted in filtered water (1:10), and G8 received Glucantime® (0.6mg/100µl of PBS), intraperitoneally. Spleen fragments were submitted to double blind histopathological evaluation and the number of megakaryocytes was counted. Besides, animals' serum was measured after 49days of infection, and cytokines (IFN-γ, IL-4, IL-10, IL-12), as well as the Th1/Th2 correlation (IFN-γ/IL-4 and IFN-γ/IL-10), were analyzed. Spleen histological parameters were classified as: healthy appearance (G1); discreet (G3-G7), moderate (G2) and moderate to severe (G8) white pulp hyperplasia; proliferation of megakaryocytes (G2-G8), and intense disruption (G2-G8). All groups, except for G7, showed higher percentages of megakaryocytes per field ranging from 87% to 15%, when compared to healthy animals (G1). Th1 predominance in IFN-γ/IL-4 ratio (comparing to G2) was detected in G4, G5, G6 and G7. Finally, pre/post (BioLi30x) and post-treatment (Antimonium crudum 30x) presented reduction of megakaryocytes/spleen changes due to immunomodulation animal process, controlling the infection process, probably by the Th1 cytokine predominance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice

    NARCIS (Netherlands)

    McBride, P. A.; Eikelenboom, P.; Kraal, G.; Fraser, H.; Bruce, M. E.

    1992-01-01

    Abnormal forms of a host protein, PrP, accumulate in the central nervous system in scrapie-affected animals. Here, PrP protein was detected immunocytochemically in tissue sections of spleen, lymph node, Peyer's patches, thymus, and pancreas from uninfected mice and from mice infected with a range of

  20. Distal splenorenal shunt with partial spleen resection

    Directory of Open Access Journals (Sweden)

    Gajin Predrag

    2007-01-01

    Full Text Available Introduction: Hypersplenism is a common complication of portal hypertension. Cytopenia in hypersplenism is predominantly caused by splenomegaly. Distal splenorenal shunt (Warren with partial spleen resection is an original surgical technique that regulates cytopenia by reduction of the enlarged spleen. Objective. The aim of our study was to present the advantages of distal splenorenal shunt (Warren with partial spleen resection comparing morbidity and mortality in a group of patients treated by distal splenorenal shunt with partial spleen resection with a group of patients treated only by a distal splenorenal shunt. Method. From 1995 to 2003, 41 patients with portal hypertension were surgically treated due to hypersplenism and oesophageal varices. The first group consisted of 20 patients (11 male, mean age 42.3 years who were treated by distal splenorenal shunt with partial spleen resection. The second group consisted of 21 patients (13 male, mean age 49.4 years that were treated by distal splenorenal shunt only. All patients underwent endoscopy and assessment of oesophageal varices. The size of the spleen was evaluated by ultrasound, CT or by scintigraphy. Angiography was performed in all patients. The platelet and white blood cell count and haemoglobin level were registered. Postoperatively, we noted blood transfusion, complications and total hospital stay. Follow-up period was 12 months, with first checkup after one month. Results In the first group, only one patient had splenomegaly postoperatively (5%, while in the second group there were 13 patients with splenomegaly (68%. Before surgery, the mean platelet count in the first group was 51.6±18.3x109/l, to 118.6±25.4x109/l postoperatively. The mean platelet count in the second group was 67.6±22.8x109/l, to 87.8±32.1x109/l postoperatively. Concerning postoperative splenomegaly, statistically significant difference was noted between the first and the second group (p<0.05. Comparing the

  1. Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin

    International Nuclear Information System (INIS)

    DeSilva, M.A.; Wepsic, H.T.; Mizushima, Y.; Nikcevich, D.A.; Larson, C.H.

    1985-01-01

    The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin

  2. The onset of hemoglobin synthesis in spleens of irradiated mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Ponka, P.; Fuchs, O.; Borova, J.; Necas, E.

    1977-01-01

    Messenger RNA (mRNA) for globin was isolated from spleens of irradiated mice in which erythroid differentiation was induced by a bone marrow graft. The globin mRNA was isolated either by means of sucrose gradients of reticulocyte polysomal RNA or by affinity chromatography of total spleen RNA on poly (U)-sepharose. The globin mRNA was tested in a wheat embryo cell-free system. The appearance of mRNA in the spleen erythroid colonies was correlated with other parameters of erythroid differentiation such as globin synthesis, activity of delta-aminolevulinic acid synthetase and iron uptake. Poly(A) containing mRNA did appear already on the 3rd day after grafting. However, significant translational activity of globin mRNA could be demonstrated only one day later together with increase in globin synthesis and delta-aminolevulinic acid synthetase and enhanced iron uptake. In the second part of this study mouse spleen cells rich in erythroid elements were incubated with a specific heme synthesis inhibitor (isonicotinic acid hydrazide, INH) and the synthesis of 9 S RNA was estimated. It was found that a 40-minute incubation with INH reduced uridine incorporation into 9 S RNA fraction by about 40%. (author)

  3. Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

    Science.gov (United States)

    Alattar, M H; Ravindranath, T M; Choudhry, M A; Muraskas, J K; Namak, S Y; Dallal, O; Sayeed, M M

    2001-01-01

    Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats. Copyright 2001 S. Karger AG, Basel

  4. Dose response relationship for unstable-type chromosome aberration rate of spleen cells from mice continuously exposed to low-dose-rate gamma-rays

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Khoda, Atsushi; Ichinohe, Kazuaki; Oghiso, Yoichi

    2007-01-01

    It has been reported that people who are chronically exposed to radiation such as nuclear facility workers and medical radiologists have slightly higher incidences of chromosome aberrations than non-exposed people. However, chronological changes of chromosome aberration rates related to accumulated doses and dose-rates for low dose-rate radiation exposures have not been well studied. Precise analyses of human populations are quite limited because confounding factors influence the results. For this reason, animal experiments are important for analyses. Mice were continuously exposed to gamma-rays at 400 mGy/22 hr/day for 10 days, 20 mGy/22 hr/day for about 400 days, and 1 mGy/22 hr/day for about 615 days under SPF conditions. Chronological changes of unstable-type chromosome aberration rates of spleen cells were observed along with accumulated doses at the middle dose rate and the two low-dose rates by conventional Giemsa-staining method. Aberrations such as dicentric chromosome, ring chromosome and fragment increased in a two-phase manner within 0-1.2 Gy and 2-8 Gy at 20 mGy/22 hr/day. They slightly increased up to 0.5 Gy at 1 mGy/22 hr/day. Aberration rates for 1, 2, 8 Gy at the 20 mGy/22 hr/day and for 0.5 Gy at 1 mGy/22 hr/day were 5.1, 9.6, 13.9 and 2.2 times higher than those of age-matched, non-irradiated control mice, respectively. Chromosome aberration rates at 400 mGy/22 hr/day were 2.7 times higher than that of 20 mGy/22 hr/day for the same total dose of 1.2 Gy. The results that unstable-type chromosome aberrations increased with accumulated dose of the low-dose rate radiation will be important to establish biological dosimetry for people who are chronically exposed to radiation. (author)

  5. Iron oxides in human spleen.

    Science.gov (United States)

    Kopáni, Martin; Miglierini, Marcel; Lančok, Adriana; Dekan, Július; Čaplovicová, Mária; Jakubovský, Ján; Boča, Roman; Mrazova, Hedviga

    2015-10-01

    Iron is an essential element for fundamental cell functions and a catalyst for chemical reactions. Three samples extracted from the human spleen were investigated by scanning (SEM) and transmission electron microscopy (TEM), Mössbauer spectrometry (MS), and SQUID magnetometry. The sample with diagnosis of hemosiderosis (H) differs from that referring to hereditary spherocytosis and the reference sample. SEM reveals iron-rich micrometer-sized aggregate of various structures-tiny fibrils in hereditary spherocytosis sample and no fibrils in hemochromatosis. Hematite and magnetite particles from 2 to 6 μm in TEM with diffraction in all samples were shown. The SQUID magnetometry shows different amount of diamagnetic, paramagnetic and ferrimagnetic structures in the tissues. The MS results indicate contribution of ferromagnetically split sextets for all investigated samples. Their occurrence indicates that at least part of the sample is magnetically ordered below the critical temperature. The iron accumulation process is different in hereditary spherocytosis and hemosiderosis. This fact may be the reason of different iron crystallization.

  6. Effect of low dose radiation on apoptosis in mouse spleen

    International Nuclear Information System (INIS)

    Chen Dong; Liu Jiamei; Chen Aijun; Liu Shuzheng

    1999-01-01

    Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis

  7. Parasite load induces progressive spleen architecture breakage and impairs cytokine mRNA expression in Leishmania infantum-naturally infected dogs.

    Science.gov (United States)

    Cavalcanti, Amanda S; Ribeiro-Alves, Marcelo; Pereira, Luiza de O R; Mestre, Gustavo Leandro; Ferreira, Anna Beatriz Robottom; Morgado, Fernanda N; Boité, Mariana C; Cupolillo, Elisa; Moraes, Milton O; Porrozzi, Renato

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease and dogs are considered the main urban reservoir of L. infantum in zoonotic VL. Infected dogs develop progressive disease with a large clinical spectrum. A complex balance between the parasite and the genetic/immunological background of the host are decisive for infection evolution and clinical outcome. This study comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso, Brazil. Spleen samples were collected for determining parasite load, humoral response, cytokine mRNA expression and histopathology alterations. By real-time PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46) and a high parasite load groups (highP, n = 42). When comparing these groups, results show variable individual humoral immune response with higher specific IgG production in infected animals but with a notable difference in CVL rapid test optical densities (DPP) between highP and lowP groups. Splenic architecture disruption was characterized by disorganization of white pulp, more evident in animals with high parasitism. All cytokine transcripts in spleen were less expressed in highP than lowP groups with a large heterogeneous variation in response. Individual correlation analysis between cytokine expression and parasite load revealed a negative correlation for both pro-inflammatory cytokines: IFNγ, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and TGFβ. TNF showed the best negative correlation (r2 = 0.231; pdogs with high parasite load associated with a structural modification in the splenic lymphoid micro-architecture. We also discuss the possible mechanism responsible for the uncontrolled parasite growth and clinical outcome.

  8. Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Morecki, S.; Weigensberg, M.; Bar, S.; Weiss, L.

    1986-01-01

    Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones

  9. Modification of radioresponse of chick spleen with vitamin E treatment

    International Nuclear Information System (INIS)

    Rana, K.; Malhotra, N.

    1995-01-01

    Seven days old white leghorn male chicks were exposed to 2.25 Gy whole body gamma radiations with and without vitamin E and studied for histopathological changes in the spleen for a period of twenty eight days postirradiation. The results reveal that the radiation-induced depletion of lymphocytic population in the lymphoid region and the damage to the tissue architecture is comparatively less and reparation of the spleen faster in the vitamin E treated irradiated chicks. (author). 12 refs., 9 figs

  10. Association of Marek's Disease induced immunosuppression with activation of a novel regulatory T cells in chickens.

    Directory of Open Access Journals (Sweden)

    Angila Gurung

    2017-12-01

    Full Text Available Marek's Disease Virus (MDV is an alphaherpesvirus that infects chickens, transforms CD4+ T cells and causes deadly lymphomas. In addition, MDV induces immunosuppression early during infection by inducing cell death of the infected lymphocytes, and potentially due to activation of regulatory T (Treg-cells. Furthermore, immunosuppression also occurs during the transformation phase of the disease; however, it is still unknown how the disease can suppress immune response prior or after lymphoma formation. Here, we demonstrated that chicken TGF-beta+ Treg cells are found in different lymphoid tissues, with the highest levels found in the gut-associated lymphoid tissue (cecal tonsil: CT, fostering an immune-privileged microenvironment exerted by TGF-beta. Surprisingly, significantly higher frequencies of TGF-beta+ Treg cells are found in the spleens of MDV-susceptible chicken lines compared to the resistant line, suggesting an association between TGF-beta+ Treg cells and host susceptibility to lymphoma formation. Experimental infection with a virulent MDV elevated the levels of TGF-beta+ Treg cells in the lungs as early as 4 days post infection, and during the transformation phase of the disease in the spleens. In contrast to TGF-beta+ Treg cells, the levels of CD4+CD25+ T cells remained unchanged during the infection and transformation phase of the disease. Furthermore, our results demonstrate that the induction of TGF-beta+ Treg cells is associated with pathogenesis of the disease, as the vaccine strain of MDV did not induce TGF-beta+ Treg cells. Similar to human haematopoietic malignant cells, MDV-induced lymphoma cells expressed high levels of TGF-beta but very low levels of TGF-beta receptor I and II genes. The results confirm that COX-2/ PGE2 pathway is involved in immunosuppression induced by MDV-lymphoma cells. Taken together, our results revealed a novel TGF-beta+ Treg subset in chickens that is activated during MDV infection and tumour

  11. Cellular Composition of the Spleen and Changes in Splenic Lysosomes in the Dynamics of Dyslipidemia in Mice Caused by Repeated Administration of Poloxamer 407.

    Science.gov (United States)

    Goncharova, N V; Shurlygina, A V; Mel'nikova, E V; Karmatskikh, O L; Avrorov, P A; Loktev, K V; Korolenko, T A

    2015-11-01

    We studied the effect of dyslipidemia induced by poloxamer 407 (300 mg/kg twice a week for 30 days) on cellular composition of the spleen and splenocyte lysosomes in mice. Changes in blood lipid profile included elevated concentrations of total cholesterol, aterogenic LDL, and triglycerides most pronounced in 24 h after the last poloxamer 407 injection; gradual normalization of lipid profile was observed in 4 days (except triglycerides) and 10 days. The most pronounced changes in the spleen (increase in organ weight and number of cells, inhibition in apoptosis, and reduced accumulation of vital dye acridine orange in lysosomes) were detected on day 4; on day 10, the indices returned to normal. Cathepsin D activity in the spleen also increased at these terms. The relationship between changes in the cellular composition of the spleen and dynamics of serum lipid profile in mice in dyslipidemia caused by repeated administrations of relatively low doses of poloxamer 407 is discussed.

  12. Intravenous delivery of HIV-based lentiviral vectors preferentially transduces F4/80+ and Ly-6C+ cells in spleen, important target cells in autoimmune arthritis

    NARCIS (Netherlands)

    Brand, B.T. van den; Vermeij, E.A.; Waterborg, C.E.J.; Arntz, O.J.; Kracht, M.; Bennink, M.B.; Berg, W.B. van den; Loo, F.A. van de

    2013-01-01

    Antigen presenting cells (APCs) play an important role in arthritis and APC specific gene therapeutic targeting will enable intracellular modulation of cell activity. Viral mediated overexpression is a potent approach to achieve adequate transgene expression levels and lentivirus (LV) is useful for

  13. Spleen: development and functional evaluation

    International Nuclear Information System (INIS)

    Sty, J.R.; Conway, J.J.

    1985-01-01

    Despite the fact that the spleen has multiple functions, only one has been widely used for evaluation of the organ by imaging techniques (phagocytosis of /sup 99m/Tc sulfur colloid). The usual splenic uptake of this radiocolloid can by used to determine the size, location, and integrity of the organ. A major use of splenic radiocolloid imaging has been in the study of congenital defects. Thus, eventration of the diaphragm, accessory spleens, splenogonadal fusion, the asplenia and polysplenia syndromes, and the wandering spleen are amenable to study by means of intravenously administered radiocolloid. Interference with the splenic uptake of radiocolloid can be either focal or generalized (as in functional asplenia). Imaging of the spleen has a major role in evaluating suspected trauma of the organ and in following its clinical course. The return of splenic function after splenectomy (splenosis or accessory spleens) can be documented by radionuclide imaging, and likely by hematologic techniques when the volume of tissue is sufficiently large. The detection of intrasplenic lesions is important in tumor staging and as an alerting sign to an ongoing process. 96 references

  14. Paradoxical effects of Auger electron-emitting 111In-DTPA-NLS-CSL360 radioimmunoconjugates on hCD45+ cells in the bone marrow and spleen of leukemia-engrafted NOD/SCID or NRG mice

    International Nuclear Information System (INIS)

    Bergstrom, Dane; Leyton, Jeffrey V.; Zereshkian, Arman; Chan, Conrad; Cai, Zhongli; Reilly, Raymond M.

    2016-01-01

    Introduction: 111 In-DTPA-NLS-CSL360 radioimmunoconjugates (RIC) recognize the overexpression of the interleukin-3 receptor α-subchain (CD123) relative to the β-subchain (CD131) on leukemia stem cells (LSC). Our aim was to study Auger electron radioimmunotherapy (RIT) of acute myeloid leukemia (AML) with 111 In-DTPA-NLS-CSL360 in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice or NOD-Rag1 null IL2rγ null (NRG) mice engrafted with CD123 + human AML-5 cells. Methods: The toxicity of three doses of 111 In-DTPA-NLS-CSL360 (3.3–4.8 MBq; 11–15 μg each) injected i.v. every two weeks was studied in non-engrafted NOD/SCID or NRG mice pre-treated with 200 cGy of γ-radiation required for AML engraftment. Engraftment efficiency of (1–5) × 10 6 cells AML-5 cells inoculated i.v. into NOD/SCID or NRG mice was assessed by flow cytometric analysis for human CD45 + (hCD45 + ) cells in the bone marrow (BM) and spleen. AML-5 engrafted mice were treated with two or three doses (3.7 MBq; 10 μg each) every two weeks of 111 In-DTPA-NLS-CSL360, non-specific 111 In-DTPA-NLS-hIgG, unlabeled CSL360 (10 μg) or normal saline. The percentage of hCD45 + cells in the BM and spleen were measured at one week after completion of treatment. Results: 111 In-DTPA-NLS-CSL360 in combination with 200 cGy of γ-radiation caused an initial transient decrease in body weight in NOD/SCID but not in NRG mice. There were no hematological, liver or kidney toxicities. The spleen exhibited 13-fold lower engraftment efficiency than the BM in NOD/SCID mice inoculated with 1 × 10 6 cells but both organs were highly (>85%) engrafted in NRG mice. Unexpectedly, 111 In-DTPA-NLS-CSL360 or non-specific 111 In-DTPA-NLS-hIgG caused a paradoxical 1.5-fold increase (P < 0.0001) in the proportion of hCD45 + cells in the BM of NOD/SCID mice compared to normal saline treated mice. 111 In-DTPA-NLS-CSL360 reduced hCD45 + cells in the spleen by 3.0-fold compared to 111 In-DTPA-NLS-hIgG (P = 0

  15. Morphophysiological changes in the splenic extracellular matrix of Leishmania infantum-naturally infected dogs is associated with alterations in lymphoid niches and the CD4+ T cell frequency in spleens.

    Directory of Open Access Journals (Sweden)

    Aurea Virginia Andrade da Silva

    2018-04-01

    Full Text Available The spleen is one of the main affected organs in canine visceral leishmaniasis (CVL. Disorganization of the splenic white pulp (SWP has been associated with immunosuppression and disease progression. This study aims to assess structural and cellular changes in the splenic extracellular matrix of dogs with CVL, correlating these changes with the parasite load and clinical signs. Splenic fragments were collected from 41 naturally infected animals for parasite load quantification by quantitative PCR, histopathological analysis and immunohistochemistry for CD3+, CD4+, and CD8+ T cells; CD21+ B cells; Ki-67+, IFN-γ+, and IL-10+ cells; and the MMP-9 and ADAM-10 enzymes. Laminin, collagen and fibronectin deposition were also evaluated. The animals were grouped according to the level of SWP organization. SWP disorganization was accompanied by a reduction in the quantity of lymphoid follicles/mm2 (p > 0.0001. Animals with moderate to intense SWP disorganization showed more clinical signs (p = 0.021, higher laminin (p = 0.045 and collagen deposition (p = 0.036, higher MMP-9 expression (p = 0.035 and lower numbers of CD4+ T cells (p = 0.027 in the spleen than the animals with organized SWP. These data suggest that splenic structure and function are drastically altered and compromised during CVL.

  16. Effects of aqueous extract of Portulaca oleracea L. on oxidative stress and liver, spleen leptin, PARα and FAS mRNA expression in high-fat diet induced mice.

    Science.gov (United States)

    Chen, Bendong; Zhou, Haining; Zhao, Wenchao; Zhou, Wenyan; Yuan, Quan; Yang, Guangshun

    2012-08-01

    We reported that an aqueous extract of Portulaca oleracea L. inhibited high-fat-diet-induced oxidative injury in a dose-dependent manner. Male kunming mice (5-weeks-old, 24 g) were used in this experiment. After a 4-day adaptation period, animals were randomly divided into four groups (n = 10 in each group); Group 1: animals received normal powdered rodent diet; Group 2: animals received high fat diet; Groups 3 and 4: animals received high fat diet and were fed by gavage to mice once a day with aqueous extract at the doses of 100 and 200 mg/kg body weight, respectively. In mice fed with high-fat diet, blood and liver lipid peroxidation level was significantly increased, whereas antioxidant enzymes activities were markedly decreased compared to normal control mice. Administration of an aqueous extract of P. oleracea L. significantly dose-dependently reduced levels of blood and liver lipid peroxidation and increased the activities of blood and liver antioxidant enzymes activities in high fat mice. Moreover, administration of an aqueous extract of P. oleracea L. significantly dose-dependently increase liver Leptin/β-actin (B), and Liver PPARα/β-actin, decrease liver, spleen FAS mRNA, p-PERK and p-PERK/PERK protein expression levels. Taken together, these data demonstrate that aqueous extract of P. oleracea L. can markedly alleviate high fat diet-induced oxidative injury by enhancing blood and liver antioxidant enzyme activities, modulating Leptin/β-actin (B), and Liver PPARα/β-actin, decrease liver, spleen FAS mRNA, p-PERK and p-PERK/PERK protein expression levels in mice.

  17. Hydatid disease of the spleen

    International Nuclear Information System (INIS)

    Sinner, W.N. von; Stridbeck, H.

    1992-01-01

    Seven patients with hydatid disease of the spleen were examined by radiography, ultrasound, CT, and in one case MR imaging. The observations were confirmed by patho-anatomic findings except in 2 patients where high indirect hemagglutination tests confirmed the diagnosis. (orig./MG)

  18. Torsion of a wandering spleen

    African Journals Online (AJOL)

    No improvement was noted on detorsion of the vascular pedicle, and a splenectomy was performed. The spleen measured 120×90×55 mm and weighed 250 g. Histological examination of the organ identified significant haemorrhagic congestion associated with diffuse haemorrhagic necrosis, with no neoplasm or infiltrate.

  19. Immunomodulation by gadolinium chloride-induced Kupffer cell phagocytosis blockade

    International Nuclear Information System (INIS)

    Lazar, G.; Husztik, E.; Kiss, I.; Szakacs, J.; Olah, J.

    1998-01-01

    Gadolinium chloride (GdCl 3 ), a rare earth metal salt, depresses macrophage activity, and is commonly used to study the physiology of the reticuloendothelial system. In the present work, the effect of GdCl 3 -induced Kupffer cell blockade on the humoral immune response in mice to sheep red blood cells (SRBC) was investigated. Kupffer cell phagocytosis blockade was found to increase both the primary and secondary immune responses to SRBC. The primary immune response was significantly augmented in animals injected intravenously with GdCl 3 2, 3 or 4 days before injection of the cellular antigen, but GdCl 3 injected 7 days before the antigen did not modify the immune response. Increased secondary humoral immune responses were also observed. When GdCl 3 was injected 2 days before the second dose of antigen, the numbers of both IgM and IgG-producing plaque forming cells were augmented. GdCl 3 injected 2 days before the first dose of SRBC did not modify the humoral immune response. Earlier studies with 51 Cr-labelled foreign red blood cells suggested that the augmentation of the humoral immune response in GdCl 3 -pretreated mice is a consequence of the spillover of the antigen from the liver into the spleen and other extrahepatic reticuloendothelial organs. (orig.)

  20. Functional assessment of hepatocytes after transplantation into rat spleen

    International Nuclear Information System (INIS)

    Woods, R.J.; Fuller, B.J.; Attenburrow, V.D.; Nutt, L.H.; Hobbs, K.E.

    1982-01-01

    The retention of structural integrity and metabolic function by isolated hepatocytes after ectopic transplantation has been investigated in autografted rats. Rats were partially hepatectomized and isolated hepatocytes prepared from the excised liver lobes were implanted into their spleens. Histological examination of the spleens 7 or more weeks after implantation revealed aggregates of hepatocytes in the red pulp. Two tests of biochemical function were applied to the hepatocytes after transplantation. In the first the hepatobiliary imaging agent technetium-99m N-[N'-(2, 6-dimethylphenyl)carbamoylmethyl]iminodiacetic acid (99mTc HIDA), which was shown to be avidly taken up by isolated hepatocytes in vitro, was infused into the tail veins of autograft and control rats. Radioactivity accumulating in the spleens of autografted rats was markedly greater than that in controls implanted with lethally damaged cells or in nontransplanted rats. In the second the presence of bilirubin metabolites was sought in autograft spleens after intravenous infusion of bilirubin. Both mono- and diglucuronides of bilirubin were recovered from the spleens of autograft rats but no conjugates were recovered from the spleens of unoperated controls. We conclude that after autotransplantation isolated hepatocytes retain their morphology and at least some of their functional activities

  1. Interleukin-12 promotes activation of effector cells that induce a severe destructive granulomatous form of murine experimental autoimmune thyroiditis.

    OpenAIRE

    Braley-Mullen, H.; Sharp, G. C.; Tang, H.; Chen, K.; Kyriakos, M.; Bickel, J. T.

    1998-01-01

    Granulomatous inflammatory lesions are a major histopathological feature of a wide spectrum of human infectious and autoimmune diseases. Experimental autoimmune thyroiditis (EAT) with granulomatous histopathological features can be induced by mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg and anti-interleukin-2 receptor (anti-IL-2R), anti-IL-2, or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibody (MAb). These studies suggested that IFN-gamma-producing T...

  2. Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: Protective role of arjunolic acid

    International Nuclear Information System (INIS)

    Manna, Prasenjit; Ghosh, Jyotirmoy; Das, Joydeep; Sil, Parames C.

    2010-01-01

    Present study investigates the beneficial role of arjunolic acid (AA) against the alteration in the cytokine levels and simultaneous activation of oxidative stress responsive signaling pathways in spleen under hyperglycemic condition. Diabetes was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body weight, injected in the tail vain). STZ administration elevated the levels of IL-2 as well as IFN-γ and attenuated the level of TNF-α in the sera of diabetic animals. In addition, hyperglycemia is also associated with the increased production of intracellular reactive intermediates resulting with the elevation in lipid peroxidation, protein carbonylation and reduction in intracellular antioxidant defense. Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IκBα and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue. Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death. Histological examination revealed that diabetic induction depleted the white pulp scoring which is in agreement with the reduced immunological response. Treatment with AA prevented the hyperglycemia and its associated pathogenesis in spleen tissue. Results suggest that AA might act as an anti-diabetic and immunomodulatory agent against hyperglycemia.

  3. Effects of multiple low dose radiation on spleen T lymphocyte subgroups in eight-week diabetic rats

    International Nuclear Information System (INIS)

    Guan Feng; Li Yanbo; Zhao Hongguang; Guo Wei; Wang Zhicheng; Gong Shouliang; Guo Caixia

    2008-01-01

    Objective: To explore the changes of spleen lymphocyte subgroups in diabetic rats after multiple low dose radiation (LDR). Methods: The experiment was divided into normal control group, pure diabetes mellitus (DM) group, and DM plus different doses of irradiation groups (the irradiation doses were 0.025, 0.050 and 0.075 Gy, respectively). The diabetic rat model was induced by intraperitoneal injection of streptozotocin. After the diabetic rats were irradiated 15 times, the percentages of spleen CD4 + and CD8 + T cells and ratio of CD4 + /CD8 + T cells were detected with flow cytometry on the fourth weekend. Results: The diabetic rats manifested obvious polydipsia, polyphagia, polyuria and weight loss. On the fourth weekend after irradiation, as compared with normal control group, the percentage of spleen CD4 + T cells increased significantly (P + T cells decreased significantly (P + /CD8 + T cells was increased significantly (P + T cells were declined markedly in both 0.050 and 0.075 Gy plus DM groups (P + T cells increased significantly in LDR plus DM groups (P + /CD8 + T cells was declined obviously (P<0.01). Conclusion: The multiple LDR could regulate the immune function in diabetic rats, and rectificate the immunological imbalance in order to protect body. (authors)

  4. Search for antisense copies of beta-globin mRNA in anemic mouse spleen

    Directory of Open Access Journals (Sweden)

    Taylor John M

    2001-03-01

    Full Text Available Abstract Background Previous studies by Volloch and coworkers have reported that during the expression of high levels of β-globin mRNA in the spleen of anemic mice, they could also detect small but significant levels of an antisense (AS globin RNA species, which they postulated might have somehow arisen by RNA-directed RNA synthesis. For two reasons we undertook to confirm and possibly extend these studies. First, previous studies in our lab have focussed on what is an unequivocal example of host RNA-directed RNA polymerase activity on the RNA genome of human hepatitis delta virus. Second, if AS globin species do exist they could in turn form double-stranded RNA species which might induce post-transcriptional gene silencing, a phenomenon somehow provoked in eukaryotic cells by AS RNA sequences. Results We reexamined critical aspects of the previous globin studies. We used intraperitoneal injections of phenylhydrazine to induce anemia in mice, as demonstrated by the appearance and ultimate disappearance of splenomegaly. While a 30-fold increase in globin mRNA was detected in the spleen, the relative amount of putative AS RNA could be no more than 0.004%. Conclusions Contrary to earlier reports, induction of a major increase in globin transcripts in the mouse spleen was not associated with a detectable level of antisense RNA to globin mRNA.

  5. Effects of Thy-1+ cell depletion on the capacity of donor lymphoid cells to induce tolerance across an entire MHC disparity in sublethally irradiated adult hosts

    International Nuclear Information System (INIS)

    Pierce, G.E.; Watts, L.M.

    1989-01-01

    Thy-1+ cell depletion with anti-Thy-1.2 mAb and complement markedly reduced the capacity of C57BL/6J, H-2b bone marrow to establish mixed lymphoid chimerism and induce tolerance to C57BL/6J skin grafts across an entire MHC disparity in BALB/c, H-2d hosts conditioned with sublethal, fractionated 7.5 Gy total-body irradiation. In this model tolerance can be transferred to secondary irradiated BALB/c hosts only by cells of C57BL/6J donor, not host, genotype isolated from the spleens of tolerant hosts. Thy-1+ cell depletion abolished the capacity of C57BL/6J donor cells from tolerant BALB/c host spleens to transfer tolerance. The capacity of semiallogeneic BALB/c x C57BL/6J F1, H-2d/b donor BM and spleen cells to induce chimerism and tolerance to C57BL/6J skin grafts in BALB/c parental hosts was also reduced by Thy-1+ cell depletion. Thus the requirement for donor Thy-1+ cells cannot be explained simply on the basis of alloaggression. It is unlikely that the requisite Thy-1+ cells are nonspecific suppressor cells: Thy-1+ cell depletion had no effect on the slight but significant prolongation of third-party C3H/HeJ, H-2k skin grafts in irradiated BALB/c hosts injected with allogeneic C57BL/6J or semiallogeneic BALB/c x C57BL/6J F1 BM compared to irradiated controls injected with medium only. Furthermore, injections of semiallogeneic F1 spleen cells had no significant effect on the survival of the third-party grafts, although these cells were fully capable of inducing tolerance, and their capacity to induce tolerance was significantly reduced by Thy-1+ cell depletion. The requirement for a specific population of lymphoid cells, i.e. Thy-1+, remains unexplained but suggests that donor cells might play a role in the induction or maintenance of tolerance in this model other than merely providing a circulating source of donor antigens

  6. Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of female C57BL/6 mice.

    Science.gov (United States)

    Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel-Baki, Abdel Azeem S; Delic, Denis; Santourlidis, Simeon; Wunderlich, Frank

    2013-11-01

    Epigenetic reprogramming of host genes via DNA methylation is increasingly recognized as critical for the outcome of diverse infectious diseases, but information for malaria is not yet available. Here, we investigate the effect of blood-stage malaria of Plasmodium chabaudi on the DNA methylation status of host gene promoters on a genome-wide scale using methylated DNA immunoprecipitation and Nimblegen microarrays containing 2,000 bp oligonucleotide features that were split into -1,500 to -500 bp Ups promoters and -500 to +500 bp Cor promoters, relative to the transcription site, for evaluation of differential DNA methylation. Gene expression was analyzed by Agilent and Affymetrix microarray technology. Challenging of female C57BL/6 mice with 10(6) P. chabaudi-infected erythrocytes resulted in a self-healing outcome of infections with peak parasitemia on day 8 p.i. These infections induced organ-specific modifications of DNA methylation of gene promoters. Among the 17,354 features on Nimblegen arrays, only seven gene promoters were identified to be hypermethylated in the spleen, whereas the liver exhibited 109 hyper- and 67 hypomethylated promoters at peak parasitemia in comparison with non-infected mice. Among the identified genes with differentially methylated Cor-promoters, only the 7 genes Pigr, Ncf1, Klkb1, Emr1, Ndufb11, and Tlr6 in the liver and Apol6 in the spleen were detected to have significantly changed their expression. Remarkably, the Cor promoter of the toll-like receptor Tlr6 became hypomethylated and Tlr6 expression increased by 3.4-fold during infection. Concomitantly, the Ups promoter of the Tlr1 was hypermethylated, but Tlr1 expression also increased by 11.3-fold. TLR6 and TLR1 are known as auxillary receptors to form heterodimers with TLR2 in plasma membranes of macrophages, which recognize different pathogen-associated molecular patterns (PAMPs), as, e.g., intact 3-acyl and sn-2-lyso-acyl glycosylphosphatidylinositols of P. falciparum

  7. Torsion of wandering spleen and distal pancreas

    International Nuclear Information System (INIS)

    Sheflin, J.R.; Lee, C.M.; Kretchmar, K.A.

    1984-01-01

    Wandering spleen is the term applied to the condition in which a long pedicle allows the spleen to lie in an abnormal location. Torsion of a wandering spleen is an unusual cause of an acute abdomen and is rarely diagnosed preoperatively. Associated torsion of the distal pancreas is even more uncommon. The authors describe a patient with torsion of a wandering spleen and distal pancreas, who was correctly diagnosed, and define the merits of the imaging methods used. The initial examination should be 99 /sup m/Tc-sulfur colloid liner-spleen scanning

  8. Cell-mediated immune response to syngeneic uv induced tumors. I. The presence of tumor associated macrophages and their possible role in the in vitro generation of cytotoxic lymphocytes

    International Nuclear Information System (INIS)

    Woodward, J.G.; Daynes, R.A.

    1978-01-01

    A primary in vitro sensitization system employing a chromium release assay was utilized to investigate reactivity of murine spleen cells toward syngeneic ultraviolet (uv) light induced fibrosarcomas. These tumors are immunologically rejected in vivo when implanted into normal syngeneic mice but grow progressively when implanted into syngeneic mice that had previously been irradiated with subcarcinogenic levels of uv light. Following appropriate sensitization, spleen cells from both normal and uv irradiated mice are capable of developing cytotoxic lymphocytes in vitro against the uv induced tumors. It was subsequently discovered that in situ uv induced tumors all contained macrophages of host origin that became demonstrable only after enzymatic dissociation of the tumor tissue. These macrophages were immunologically active in vitro as their presence in the stimulator cell population was necessary to achieve an optimum anti-tumor cytotoxic response following in vitro sensitization. Anti-tumor reactivity generated by mixing spleen cells and tumor cells in the absence of tumor derived macrophages could be greatly enhanced by the addition of normal syngeneic peritoneal macrophages. When in vitro anti-tumor reactivity of spleen cells from normal and uv treated mice was compared under these conditions we again found no significant difference in the magnitude of the responses. In addition, the cytotoxic cells generated in response to uv induced tumors appeared to be highly cross reactive with respect to their killing potential

  9. Trypanosoma cruzi: Serum levels of nitric oxide and expression of inducible nitric oxide synthase in myocardium and spleen of dogs in the acute stage of infection with metacyclic or blood trypomastigotes.

    Science.gov (United States)

    Vieira, Paula Melo de Abreu; Francisco, Amanda Fortes; de Souza, Sheler Martins; Malaquias, Luiz Cosme Cotta; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro; Veloso, Vanja Maria; de Lana, Marta; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2009-01-01

    The participation of nitric oxide (NO) in the control of blood parasitemia and parasitism during the acute phase of infection in dogs inoculated with blood trypomastigotes (BT) or metacyclic trypomastigotes (MT group) of Berenice-78 Trypanosoma cruzi strain has been evaluated. Animals of the MT group (n=4) presented increased levels of serum NO throughout the infection when compared with the BT (n=4) or control (n=4) groups, and a delay in parasitemia peak compared with the BT group. In spleen fragments, tissue parasitism was not observed but the MT group presented larger areas associated with inducible NO synthase (iNOS) in relation to BT and control groups. Heart fragments of MT-infected animals exhibited comparatively low tissue parasitism and high iNOS expression, while animals of the BT group presented high inflammatory infiltrate, high tissue parasitism and low iNOS expression. These results indicate that the source of inoculum can interfere with the development of the acute phase of Chagas disease, and may also trigger a distinct parasite-host interaction during this phase.

  10. [Ultrasound of spleen and retroperitoneum].

    Science.gov (United States)

    Salcedo Joven, I; Segura-Grau, A; Díaz Rodríguez, N; Segura-Cabral, J M

    2016-09-01

    Ultrasound provides data of extremely great value when studying spleen pathology, being diagnostic in splenomegaly and splenic trauma, as well as offering a good approach to the diagnosis of both benign and malignant focal pathology, particularly lymphoma. However, for the evaluation of adrenal and retroperitoneal diseases, other techniques such as CT or MRI are more suitable, even though ultrasound is still an excellent screening and monitoring method, as well as being useful in non-invasive therapeutic approaches. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Effect of interleukin-2 on cell proliferation, sister-chromatid exchange induction, and nuclear stress protein phosphorylation in PHA-stimulated Fischer 344 rat spleen lymphocytes: Modulation by 2-mercaptoethanol

    Energy Technology Data Exchange (ETDEWEB)

    Morris, S.M.; Aidoo, A.; Domon, O.E.; McGarrity, L.J.; Kodell, R.L.; Schol, H.M.; Hinson, W.G.; Pipkin, J.L.; Casciano, D.A. (National Center for Toxicological Research, Jefferson, AR (USA))

    1990-01-01

    The effect of interleukin-2 (IL-2) on cell proliferation, sister-chromatid exchange (SCE) frequency, and the phosphorylation of nuclear stress proteins was evaluated in phytohemagglutinin (PHA)-stimulated spleen lymphocytes isolated from Fischer 344 rats. In addition, the ability of 2-mercaptoethanol (2-ME) to modulate the induction of these biological responses was characterized. Cell proliferation, as measured by the mitotic index, increased significantly. The average generation time (AGT) did not respond to IL-2 in a concentration-dependent manner and decreased significantly. The number of SCE increased significantly from control frequencies, to frequencies of 18.5 to 21.5 SCE per cell as the concentration of IL-2 in the culture medium increased to 50 half-maximal units per ml. A reduction in SCE frequency was observed when cells were cultured with 20 {mu}M 2-ME and IL-2 compared to IL-2 alone. Three nuclear proteins, with relative molecular masses of approximately 13,000-18,000, 20,000, and 80,000, were phosphorylated in IL-2-exposed G{sub 1}-phase nuclei. Elicitation of these nuclear proteins in IL-2-exposed cells was not affected by exposure to 2-ME.

  12. Role of the spleen in the maturation of B-lymphocytes

    International Nuclear Information System (INIS)

    Strober, S.

    1976-01-01

    Spleen cells from unimmunized Lewis rats were fractionated by 1 x g velocity sedimentation and assayed for their ability to restore the adoptive primary antibody response to horse spleen ferritin in irradiated syngeneic recipients given T cell supplementation. Large, medium and small cell fractions all showed virgin B cell activity. Similar studies with thoractic duct cells show that virgin B cell activity is restricted to the small and medium cells. Large spleen cells produced a 2-ME sensitive adoptive antibody response which persisted for 21 days. All antibody produced by small cells at 21 days was 2-ME resistant. Examination of spleen cells during recovery from sublethal irradiation showed that virgin B cell activity was first detected at 14 days, and is confined to the large cell fraction. Experiments with congenic rats which differ at the immunoglobulin (Ig) light chain allotype showed that small cells from the bone marrow injected intravenously can transform into large Ig-bearing cells in the spleen. The relationship of the subclasses of virgin B cells in the spleen to B cell maturation is discussed

  13. Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling.

    Science.gov (United States)

    Huang, Xiaohong; Huang, Youhua; Ouyang, Zhengliang; Xu, Lixiao; Yan, Yang; Cui, Huachun; Han, Xin; Qin, Qiwei

    2011-08-01

    Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genus Ranavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow, FHM) cells, as evidenced by caspase activation and DNA fragmentation, suggesting that SGIV infection induced nonapoptotic cell death by a cell type dependent fashion. Furthermore, viral replication was essential for SGIV induced nonapoptotic cell death, but not for apoptosis. Notably, the disruption of mitochondrial transmembrane potential (ΔΨm) and externalization of phosphatidylserine (PS) were not detected in EAGS cells but in FHM cells after SGIV infection. Moreover, the extracellular signal-regulated kinase (ERK) signaling was involved in SGIV infection induced nonapoptotic cell death and viral replication. This is a first demonstration of ERK-mediated nonapoptotic cell death induced by a DNA virus. These findings contribute to understanding the mechanisms of iridovirus pathogenesis.

  14. Study of microflora status of radiation-induced peripheral blood T cell and its subgroup changes

    International Nuclear Information System (INIS)

    Ding Hao; Wang Shengzi; Wang Shuyi; Lu Shenbin; Guo Ming; Tian Jie

    2009-01-01

    Objective: To observe the differences of the radiation-induced peripheral blood T cell and its subgroup changes between SPF and CV rats after nasopharyngeal radiation with gradient doses and explore the microflora factors in the pathogenesis of abnormal radiation-induced immunity status. Methods: 8 from each SPF and CV rats were chosen for oropharyngeal bacteria cultivation and determination and the spleen organ coefficients. The rest were irradiated with 6MX linear accelerator in the nasopharyngeal fields at dose of 0, 10, 20, 30 Gy, 5 in each group. 24 ∼ 36 h later, blood T lymphocytes and their subgroups were detected by FCM. Results: The bacteria of CV rats were pathogen mostly and the one from SPF rats was Proteus mirabilis uniquely. Spleen organ coefficients between two groups showed no statistical difference. CD + 3 , CD + 4 lymphocytes and the ratio of CD + 4 / CD + 8 of CV rats decreased dramatically after radiation is in close relation with radiation doses while The CD + 8 lymphocyte increased a bit. The CD + 3 , CD + 4 , CD + 8 lymphocytes and the ratio of CD + 4 / CD + 8 of SPF rats remained in a stable level. Conclusions: There exists the difference of radiation-induced injuries of immune system in relation with different microflora status. Micro-flora plays an important role in the radiation-induced immune system abnormity. (authors)

  15. Modulation of macrophage Ia expression by lipopolysaccharide: Stem cell requirements, accessory lymphocyte involvement, and IA-inducing factor production

    International Nuclear Information System (INIS)

    Wentworth, P.A.; Ziegler, H.K.

    1989-01-01

    The mechanism of induction of murine macrophage Ia expression by lipopolysaccharide (LPS) was studied. Intraperitoneal injection of 1 microgram of LPS resulted in a 3- to 10-fold increase in the number of IA-positive peritoneal macrophages (flow cytometry and immunofluorescence) and a 6-to 16-fold increase by radioimmunoassay. The isolated lipid A moiety of LPS was a potent inducer of macrophage Ia expression. Ia induction required a functional myelopoietic system as indicated by the finding that the response to LPS was eliminated in irradiated (900 rads) mice and reinstated by reconstitution with bone marrow cells. Comparison of LPS-induced Ia expression in normal and LPS-primed mice revealed a faster secondary response to LPS. The memory response could be adoptively transferred to normal mice with nonadherent spleen cells prepared 60 days after LPS injection. Spleen cells prepared 5 days after LPS injection caused Ia induction in LPS-nonresponder mice; such induction was not observed in irradiated (900 rads) recipients. The cell responsible for this phenomenon was identified as a Thy-1+, immunoglobulin-negative nonadherent cell. The biosynthesis and expression of Ia were not increased by direct exposure of macrophages to LPS in vitro. Small amounts of LPS inhibited Ia induction by gamma interferon. LPS showed positive regulatory effects on Ia expression by delaying the loss of Ia expression on cultured macrophages and by stimulating the production of Ia-inducing factors. Supernatants from cultured spleen cells stimulated with LPS in vitro contained antiviral and Ia-inducing activity that was acid labile, indicating that the active factor is gamma interferon. We conclude that induction of Ia expression by LPS in vivo is a bone-marrow-dependent, radiation-sensitive process which involves the stimulation of a gamma interferon-producing accessory lymphocyte and a delay in Ia turnover

  16. Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

    Directory of Open Access Journals (Sweden)

    Ina Bähr

    2017-01-01

    Full Text Available Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.

  17. Giant Accessory Right-Sided Suprarenal Spleen in Thalassaemia

    Directory of Open Access Journals (Sweden)

    A. Arra

    2013-01-01

    Full Text Available An accessory spleen is defined as ectopic splenic tissue that develops due to failure of fusion of cells during embryonic development as they migrate from the midline to the left upper quadrant. While benign, complications may arise which include trauma, torsion, or infarction of the ectopic tissue. Additionally, patients who have had a splenectomy secondary to treatment for previous pathology such as a haematological malignancy or idiopathic thrombocytopenia purpura may experience persistent symptoms due to the accessory splenic tissue. The presence of an accessory spleen is therefore of significant diagnostic and therapeutic importance. To the best of the authors' knowledge, this case is the second and largest reported case of a giant right suprarenal accessory spleen and highlights the difficulty in differentiation of these masses from malignant adrenal tumours.

  18. The effect of Echinococcus granulosus on spleen cells and TGF-β expression in the peripheral blood of BALB/c mice.

    Science.gov (United States)

    Yin, S; Chen, X; Zhang, J; Xu, F; Fang, H; Hou, J; Zhang, X; Wu, X; Chen, X

    2017-03-01

    Cystic echinococcosis (CE) caused by the cestode Echinococcus granulosus (E. granulosus) is a zoonotic parasitic disease. The effective immune evasion mechanisms of E. granulosus allow it to parasitize its hosts. However, the status of the innate and adaptive immune cells and their contributions to E. granulosus progression remain poorly understood. In this study, we aimed to determine the impact of E. granulosus infection on T cells, NK cell responses and TGF-β expression during the early infection phase in BALB/c mice. In E. granulosus infections, there was an increasing tendency in the percentage of CD4 + CD25 + T cells and CD4 + Foxp3 + T cells and peripheral blood TGF-β levels and relative expression of the Foxp3 gene. Moreover, there were a decreasing tendency in the percentage of NK cells and NK cell cytotoxicity and the expression of NKG2D on NK cells. The TGF-β1/Smad pathway was activated by E. granulosus in mice. Above results can be reversed by the inhibitor SB-525334 (potent activin receptor-like kinase 5 inhibitor). These results suggest that the TGF-β/Smad pathway plays an important role in changes of T-cell or NK cell responses. These results may contribute to revealing the preliminary molecular mechanisms in establishing hydatid infection. © 2017 John Wiley & Sons Ltd.

  19. Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression.

    Science.gov (United States)

    Han, Yanmei; Liu, Qiuyan; Hou, Jin; Gu, Yan; Zhang, Yi; Chen, Zhubo; Fan, Jia; Zhou, Weiping; Qiu, Shuangjian; Zhang, Yonghong; Dong, Tao; Li, Ning; Jiang, Zhengping; Zhu, Ha; Zhang, Qian; Ma, Yuanwu; Zhang, Lianfeng; Wang, Qingqing; Yu, Yizhi; Li, Nan; Cao, Xuetao

    2018-04-19

    Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, how primary tumor-induced non-leukocyte populations in distal organs contribute to systemic spread remains poorly defined. Here, we report one population of tumor-inducible, erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119 + CD45 - CD71 + phenotype. Ter-cells are enriched in the enlarged spleen of hosts bearing advanced tumors and facilitate tumor progression by secreting neurotrophic factor artemin into the blood. Transforming growth factor β (TGF-β) and Smad3 activation are important in Ter-cell generation. In vivo blockade of Ter-cell-derived artemin inhibits hepatocellular carcinoma (HCC) growth, and artemin deficiency abolishes Ter-cells' tumor-promoting ability. We confirm the presence of splenic artemin-positive Ter-cells in human HCC patients and show that significantly elevated serum artemin correlates with poor prognosis. We propose that Ter-cells and the secreted artemin play important roles in cancer progression with prognostic and therapeutic implications. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. MORPHOLOGICAL VARIATIONS OF SPLEEN: A CADAVERIC STUDY

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    Siva Chidambaram

    2015-07-01

    Full Text Available The Spleen is a large lymphoid organ situated in the left hypochondrial region having an important role in immunological and hematological functions of the human body. The aim of this study was to find the morphological variations of the spleen with respect to it’s a Shape, b Number of notches on its borders and c Presence of anomalous fissure on its surface. The Study was done on 60 formalin fixed cadaveric spleen from the Department of Anatomy, Narayana Medical College, Nellore, Andhra Pradesh. Out of 60 spleens we examined, the various shapes of the spleen were noted suc h as wedge shape (73.33%, triangular (13.33%, tetrahedral (6.67% and oval shape(6.67%.The number of spleen showing notches on its superior border was 38(63.33% and in inferior border it was 6(10%. Absence of splenic notch was observed in 10(16.67% s pleens and the remaining 6 spleens (10% shows notches on its both the borders. The anomalous splenic fissure was found in 4(6.67% spleens on its diaphragmatic surface. The knowledge of variations in the morphology of spleen are essential for physician, s urgeon, radiologist and forensic surgeon to differentiate it from the splenic pathology and splenic injury. In addition to this, it is also important for anatomist during routine classroom dissection and discussion.

  1. Advances in reprogramming somatic cells to induced pluripotent stem cells.

    Science.gov (United States)

    Patel, Minal; Yang, Shuying

    2010-09-01

    Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.

  2. Response of immunocompetent cells of bone marrow and spleen of mouse males of several strains to stress and to pyrazine containing chemosignals

    Directory of Open Access Journals (Sweden)

    Eugene V Daev

    2012-06-01

    Full Text Available The quantity of antibody producing cells and mitotic disturbances in dividing bone marrow cells of mice were studied after exposure of animals to a physical stressor or various pyrazinecontaining chemosignals. Several different strains of mice were used. We demonstrate that immune suppression and destabilization of the chromosome apparatus in dividing cells depend on: а mouse genotype and b side chains position  in the pyrazine ring. Importance of this effects in the light of wide usage of pyrazine containing substances in perfume industry, food production and pharmacology is discussed.

  3. High levels of circulating triiodothyronine induce plasma cell differentiation.

    Science.gov (United States)

    Bloise, Flavia Fonseca; Oliveira, Felipe Leite de; Nobrega, Alberto Félix; Vasconcellos, Rita; Cordeiro, Aline; Paiva, Luciana Souza de; Taub, Dennis D; Borojevic, Radovan; Pazos-Moura, Carmen Cabanelas; Mello-Coelho, Valéria de

    2014-03-01

    The effects of hyperthyroidism on B-cell physiology are still poorly known. In this study, we evaluated the influence of high-circulating levels of 3,5,3'-triiodothyronine (T3) on bone marrow, blood, and spleen B-cell subsets, more specifically on B-cell differentiation into plasma cells, in C57BL/6 mice receiving daily injections of T3 for 14 days. As analyzed by flow cytometry, T3-treated mice exhibited increased frequencies of pre-B and immature B-cells and decreased percentages of mature B-cells in the bone marrow, accompanied by an increased frequency of blood B-cells, splenic newly formed B-cells, and total CD19(+)B-cells. T3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220(+) cells correlating with an increased percentage of CD138(+) plasma cells was observed in the spleen and bone marrow of T3-treated mice. Using enzyme-linked immunospot assay, an increased number of splenic immunoglobulin-secreting B-cells from T3-treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or together with treatment with T3. In conclusion, we provide evidence that high-circulating levels of T3 stimulate plasma cytogenesis favoring an increase in plasma cells in the bone marrow, a long-lived plasma cell survival niche. These findings indicate that a stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.

  4. Detection of early gamma-postirradiation effects in murine spleen by proton NMR relaxation times.

    Science.gov (United States)

    Zebrowska, G; Lewa, C J; Ramee, M P; Husson, F; De Certaines, J D

    2001-01-01

    It was our aim to evaluate the potential of proton relaxation times for the early detection of radiation-induced spleen changes. Female Swiss mice were irradiated with doses ranging from 0.05 Gy to 4 Gy. The body weight, the spleen weight and the spleen water content of single animals were determined. Measurements of longitudinal (T1) and transversal (T2) proton relaxation times of the spleen samples were performed in a 0.47 T spectrometer. Histological examinations of the control and irradiated organs were performed. NMR measurements during the first five days after irradiation showed that total body gamma-irradiation with doses from 1.5 Gy to 4 Gy results in decreasing T1 of the murine spleen. Significant shortening in T2 was observed for the spleen of animals irradiated with a dose of 4 Gy. Histological examinations demonstrated subnormal architecture in slices derived from animals irradiated with 2 Gy and 4 Gy. The fluctuations of the spleen T1 and T2 of irradiated mice are correlated with relative spleen weight and can be used to estimate radiation induced changes in this organ.

  5. Induced Pluripotent Stem Cells for Regenerative Medicine

    OpenAIRE

    Hirschi, Karen K.; Li, Song; Roy, Krishnendu

    2014-01-01

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies...

  6. Merkel Cell Polyomavirus Small T Antigen Induces Cancer and Embryonic Merkel Cell Proliferation in a Transgenic Mouse Model.

    Science.gov (United States)

    Shuda, Masahiro; Guastafierro, Anna; Geng, Xuehui; Shuda, Yoko; Ostrowski, Stephen M; Lukianov, Stefan; Jenkins, Frank J; Honda, Kord; Maricich, Stephen M; Moore, Patrick S; Chang, Yuan

    2015-01-01

    Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre-mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days. Conversely, most adult UbcCreERT2; ROSAsT mice survived low-dose tamoxifen administration but developed ear lobe dermal hyperkeratosis and hypergranulosis. Simultaneous MCV sT expression and conditional homozygous p53 deletion generated multi-focal, poorly-differentiated, highly anaplastic tumors in the spleens and livers of mice after 60 days of TMX treatment. Mouse embryonic fibroblasts from these mice induced to express MCV sT exhibited anchorage-independent cell growth. To examine Merkel cell pathology, MCV sT expression was also induced during mid-embryogenesis in Merkel cells of Atoh1CreERT2/+; ROSAsT mice, which lead to significantly increased Merkel cell numbers in touch domes at late embryonic ages that normalized postnatally. Tamoxifen administration to adult Atoh1CreERT2/+; ROSAsT and Atoh1CreERT2/+; ROSAsT; p53flox/flox mice had no effects on Merkel cell numbers and did not induce tumor formation. Taken together, these results show that MCV sT stimulates progenitor Merkel cell proliferation in embryonic mice and is a bona fide viral oncoprotein that induces full cancer cell transformation in the p53-null setting.

  7. NK cell activite in C157BL/Ka mice during the development of radiation induced thymic lymphomas

    International Nuclear Information System (INIS)

    Noel, A.; Schaaf-Lafontaine, N.; Defresne, M.P.; Boniver, J.

    1985-01-01

    Treatment of C57BL/Ka mice with a split dose whole-body irradiation (four weekly irradiations of 1,75 Gy) induces the development of thymic lymphomas. NK activity of spleen cells has been determined at several internals after leukemogenic treatment. Two days after irradiations, NK activity is normal and decreases strongly after one week. This period of decline persists during about one month. Then, NK activity restores and reaches control values. Lymphomas appear in spite of NK activity restauration. The diminution of NK activity during the preleukemic period could favour preleukemic cells apparition [fr

  8. Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

    Science.gov (United States)

    Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

    2017-01-01

    Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

  9. In-vivo effects of lipopolysaccharide on lymphoid and non-lymphoid cells in the mouse spleen. Migration of marginal metallophils towards the follicle centres

    NARCIS (Netherlands)

    Groeneveld, P. H.; van Rooijen, N.; Eikelenboom, P.

    1983-01-01

    In mice marginal metallophils are located at the periphery of the white pulp along the inner border of the marginal sinus. These cells have a weak phagocytic capacity but their function is still unclear. In the present study evidence is given that marginal metallophils migrate from the periphery of

  10. Plasmodium berghei: immunosuppression of the cell-mediated immune response induced by nonviable antigenic preparations

    International Nuclear Information System (INIS)

    Gross, A.; Frankenburg, S.

    1989-01-01

    In this work, plasmodial antigens were examined for their ability to suppress the cellular immune response during lethal Plasmodium berghei infection. Splenic enlargement and the number and function of white spleen cells were assessed after injection of normal mice with irradiated parasitized erythrocytes (IPE) or with parasitized erythrocytes (PE) membranes. Both IPE and PE membranes caused splenomegaly and an increase in the number of splenic white cells with concurrent alteration of the relative proportions of T cells and macrophages. The percentage of T lymphocytes was fractionally diminished, but there was a marked increase in Lyt 2.2 positive (suppressor and cytotoxic) T subsets and in the number of splenic macrophage precursors. The pathological enlargement of the spleen was induced by various plasma membrane-derived antigens containing both proteins and carbohydrates. Splenocytes of mice injected with liposomes containing deoxycholate-treated PE or PE fractions showed both diminished interleukin 2 production and a decreased response to mitogen. It appears that some of the changes in the cellular immune response during P. berghei infection are a consequence of the massive provision of a wide spectrum of antigens, capable of suppressing the immune response. Thus, it may be appropriate to evaluate the possible negative effect of parasite epitopes that are candidates for vaccine

  11. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    Science.gov (United States)

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

  12. Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice

    International Nuclear Information System (INIS)

    Bestak, Rosa; Halliday, G.M.

    1996-01-01

    It has previously been demonstrated that chronic low-dose solar-simulated UV radiation could induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. In this study, we have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/HeJ mice. Irradiation with UVA+B significantly suppressed the local and systemic primary contact hypersensitivity (CHS) response to the hapten 2,4,6-trinitrochlorobenzene. Furthermore, UVA+B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) densities in chronically UV-irradiated mice. Ultraviolet A irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with both UVA+B and UVA radiation also induced an impaired secondary CHS response, and this tolerance was transferable with spleen cells. (Author)

  13. Cell fusion induced by ionizing radiation in various cell lines

    International Nuclear Information System (INIS)

    Khair, M.B.

    1994-07-01

    Cell fusion induced by ionizing radiation has been studied in rat's hepatocytes in vivo and in different cell lines in vitro. These cell lines were: Hela cells, V-79 fibroblasts, human and rat lymphocytes. For irradiation, 0.85 MeV fission neutrons and 14 MeV fast neutrons were used. Cell analyses were performed by fluorescent dyes using immunofluorescent microscope and flow cytometre. Our results in vivo showed that, regardless the dose-rate, a dose of 1 Gy approximately was enough to induce a significant level of cell fusion depending on neutron energy and the age of rats. The level of cell fusion was also significant in Hela cells at a dose of 0.5 Gy. Similar effect, but to a lesser extent, was observed in V-79 cells. Whereas, in lymphocytes insignificant cell fusion was noticed. The varying levels of cell-fusion in different cell lines could be attributed to the type of cells and mutual contact between cells. Furthermore irradiation did not show any influence on cell division ability in both hepatocytes and Hela cells and that fused cells were also able to divide forming a new generation of cells. (author). 36 refs., 8 figs., 10 tabs

  14. In Vivo Bystander Effect: Cranial X-Irradiation Leads to Elevated DNA Damage, Altered Cellular Proliferation and Apoptosis, and Increased p53 Levels in Shielded Spleen

    International Nuclear Information System (INIS)

    Koturbash, Igor; Loree, Jonathan; Kutanzi, Kristy; Koganow, Clayton; Pogribny, Igor; Kovalchuk, Olga

    2008-01-01

    Purpose: It is well accepted that irradiated cells may 'forward' genome instability to nonirradiated neighboring cells, giving rise to the 'bystander effect' phenomenon. Although bystander effects were well studied by using cell cultures, data for somatic bystander effects in vivo are relatively scarce. Methods and Materials: We set out to analyze the existence and molecular nature of bystander effects in a radiation target-organ spleen by using a mouse model. The animal's head was exposed to X-rays while the remainder of the body was completely protected by a medical-grade shield. Using immunohistochemistry, we addressed levels of DNA damage, cellular proliferation, apoptosis, and p53 protein in the spleen of control animals and completely exposed and head-exposed/body bystander animals. Results: We found that localized head radiation exposure led to the induction of bystander effects in the lead-shielded distant spleen tissue. Namely, cranial irradiation led to increased levels of DNA damage and p53 expression and also altered levels of cellular proliferation and apoptosis in bystander spleen tissue. The observed bystander changes were not caused by radiation scattering and were observed in two different mouse strains; C57BL/6 and BALB/c. Conclusion: Our study proves that bystander effects occur in the distant somatic organs on localized exposures. Additional studies are required to characterize the nature of an enigmatic bystander signal and analyze the long-term persistence of these effects and possible contribution of radiation-induced bystander effects to secondary radiation carcinogenesis

  15. Drosophila Ninjurin A induces nonapoptotic cell death.

    Directory of Open Access Journals (Sweden)

    Sarah Broderick

    Full Text Available Ninjurins are conserved transmembrane proteins that are upregulated across species in response to injury and stress. Their biological functions are not understood, in part because there have been few in vivo studies of their function. We analyzed the expression and function of one of three Drosophila Ninjurins, NijA. We found that NijA protein is redistributed to the cell surface in larval immune tissues after septic injury and is upregulated by the Toll pathway. We generated a null mutant of NijA, which displayed no detectable phenotype. In ectopic expression studies, NijA induced cell death, as evidenced by cell loss and acridine orange staining. These dying cells did not display hallmarks of apoptotic cells including TUNEL staining and inhibition by p35, indicating that NijA induced nonapoptotic cell death. In cell culture, NijA also induced cell death, which appeared to be cell autonomous. These in vivo studies identify a new role for the Ninjurin family in inducing nonapoptotic cell death.

  16. Indolent B-Cell Lymphoid Malignancy in the Spleen of a Man Who Handled Benzene: Splenic Marginal Zone Lymphoma

    Directory of Open Access Journals (Sweden)

    Jihye Lee

    2017-09-01

    Full Text Available We present the case of a 45-year-old man with a history of benzene exposure who developed splenic marginal zone lymphoma. For 6 years, he had worked in an enclosed space cleaning instruments with benzene. He was diagnosed with splenic marginal zone lymphoma 19 years after retirement. During his time of working in the laboratory in the 1980s, working environments were not monitored for hazardous materials. We indirectly estimated the cumulative level of past benzene exposure using job-exposure matrices and technical assumptions. Care must be taken in investigating the relevance of occupational benzene exposure in the occurrence of indolent B-cell lymphoma. Because of the long latency period and because occupational measurement data do not exist for the period during the patient's exposure, the epidemiological impact of benzene exposure may be underestimated.

  17. Competitive proliferation in the hematopoietic tissues of irradiated hybrid mice engrafted with parental bone marrow and spleen

    International Nuclear Information System (INIS)

    Muramatsu, S.; Monnot, P.; Duplan, J.F.

    1976-01-01

    e kinetics of growth and differentiation of hematopoietic stem cells differ markedly according to their origin. A study of the ability of CFU from bone marrow (BM) or spleen to repopulate hemopoietic organs has been carried out in lethally irradiated mice restored with BM cells admixed with spleen cells bearing different chromosomal markers. Hemopoietic cells originating from AKR (40 acbrocentrics) and AKR/T1ALD (36 acrocentrics + 2 metacentrics) mice were engrafted into lethally irradiated (AKR x AKR/T1ALD)F1 or (C3H x AKR/T1ALD)F1 hybrid recipients. Within 10 days, the BM-derived elements outnumbered the spleen-derived population in BM and spleen. This held even when the number of injected spleen-CFU was twice that of BM-CFU. This difference of growth rate subsided within 20 days. The first cells to reappear in the thymus bore the recipient karyotype (endoregeneration); they were later replaced by BM-derived elements but spleen-derived cecells were never present in thymus in the case of competitive engraftment. In contrast, the lymph node cells bore the BM karyotype as well as the spleen karyotype. Injecting the spleen cells 3 days prior to the BM cells partially counterbalanced the overgrowth of the BM-derived elements in the BM and spleen but did not affect the thymic repopulation which remained strictly derived from BM-CFU. When mice were injected only with BM-CFU, or only with spleen-CFU, BM-derived cells were found in the thymus as early as 10-12 days after engraftment, whereas the spleen-derived cells did not appear in the thymus until days 18-20. (author)

  18. On the effect of small radiation doses: Desoxyribonucleic acid (DNA) synthesis and DNA repair of thymus, spleen, and bone marrow cells in the rat after fractionated total body X-ray irradiation. Zur Wirkung kleiner Strahlendosen: Desoxyribonukleinsaeure-(DNA-)Synthese und DNA-Reparatur von Thymus-, Milz- und Knochenmarkszellen der Ratte nach fraktionierter Ganzkoerperroentgenbestrahlung

    Energy Technology Data Exchange (ETDEWEB)

    Tempel, K.; Ehling, G. (Muenchen Univ. (Germany, F.R.). Inst. fuer Pharmakologie, Toxikologie und Pharmazie)

    1989-09-01

    After three to seven days following to fractionated total body X-ray irradiation (TBI) (four expositions with doses of 0.3 to 5.0 cGy per fraction at intervals of 24 hours), a maximum 50 percent stimulation of the semiconservative DNA synthesis (SDS) of spleen cells was measured in vitro. This was not dependent of the fact if an acute high-dose (400 and/or 800 cGy) unique irradiation was applied after the fractionated TBI at the moment of stimulation. A significant increase of {sup 3}H-thymidine incorporation into the DNA of bone marrow and thymus cells was only found when doses of 1.25 cGy per fraction had been used. After fractionated TBI with doses of {ge}5 cGy per fraction, an increase of DNA synthesis resistant to hydroxyurea ('unprogrammed' DNA synthesis, UDS) was demonstrated in spleen cells. The UV-simulated UDS decreased proportionately. The sedimentation of thymus, spleen, and bone marrow nucleoids in a neutral saccharose gradient gave no evidence of an increased DNA repair capacity after fractionated TBI. Whereas the SDS stimulation by fractionated TBI with small doses can be explained by a modified proliferation behavior of exposed cells, the UDS behavior of spleen cells after considerably higher radiation doses suggests regenerative processes correlated with an increased number of cells resistant to hydroxyurea and cells presenting an UV repair deficiency. These findings can be considered to be a further proof of the assumed immune-stimulating effect of small radiation doses. (orig.).

  19. Cell-mediated immune responses in the head-associated lymphoid tissues induced to a live attenuated avian coronavirus vaccine.

    Science.gov (United States)

    Gurjar, Rucha S; Gulley, Stephen L; van Ginkel, Frederik W

    2013-12-01

    Humoral immunity is important for controlling viral diseases of poultry, but recent studies have indicated that cytotoxic T cells also play an important role in the immune response to infectious bronchitis virus (IBV). To better understand the cell mediated immune responses to IBV in the mucosal and systemic immune compartments chickens were ocularly vaccinated with IBV. This induced a lymphocyte expansion in head-associated lymphoid tissues (HALT) and to a lesser extent in the spleen, followed by a rapid decline, probably due to homing of lymphocytes out of these organs and contraction of the lymphocyte population. This interpretation was supported by observations that changes in mononuclear cells were mirrored by that in CD3(+)CD44(+) T cell abundance, which presumably represent T effector cells. Increased interferon gamma (IFN-γ) expression was observed in the mucosal immune compartment, i.e., HALT, after primary vaccination, but shifted to the systemic immune compartment after boosting. In contrast, the expression of cytotoxicity-associated genes, i.e., granzyme A (GZMA) and perforin mRNA, remained associated with the HALT after boosting. Thus, an Ark-type IBV ocular vaccine induces a central memory IFN-γ response in the spleen while the cytotoxic effector memory response, as measured by GZMA and perforin mRNA expression, remains associated with CALT after boosting. Copyright © 2013. Published by Elsevier Ltd.

  20. Spleen-lung interface as diagnostic information

    International Nuclear Information System (INIS)

    DeLuca, S.A.; Kolodny, G.M.

    1975-01-01

    Left anterior, lateral, and posterior views on 50 consecutive /sup 99m/Tc-sulfur colloid lung scans were examined. Normal patients had continuity of activity between the left lung and the spleen on all three views. Patients with subphrenic abscess or large left pleural effusions showed no continuity between lung and spleen activity on any view, while other abnormalities, most commonly cardiomegaly, accounted for lack of lung-spleen continuity on the anterior view only. It is suggested that in all combined /sup 99m/Tc-sulfur colloid lung studies, the left side be examined as well as the right for abnormalities adjacent to the left diaphragm. (auth)

  1. Promotion of initiated cells by radiation-induced cell inactivation.

    Science.gov (United States)

    Heidenreich, W F; Paretzke, H G

    2008-11-01

    Cells on the way to carcinogenesis can have a growth advantage relative to normal cells. It has been hypothesized that a radiation-induced growth advantage of these initiated cells might be induced by an increased cell replacement probability of initiated cells after inactivation of neighboring cells by radiation. Here Monte Carlo simulations extend this hypothesis for larger clones: The effective clonal expansion rate decreases with clone size. This effect is stronger for the two-dimensional than for the three-dimensional situation. The clones are irregular, far from a circular shape. An exposure-rate dependence of the effective clonal expansion rate could come in part from a minimal recovery time of the initiated cells for symmetric cell division.

  2. Effect of bone marrow depletion on prostaglandin E-producing suppressor macrophages in mouse spleen

    International Nuclear Information System (INIS)

    Shibata, Y.; Volkman, A.

    1985-01-01

    The i.p. injection of Corynebacterium parvum (CP) into CBA/J mice effected increases in macrophage colony-forming cells (M-CFC) when spleen cells were cultured with L cell culture filtrate as a source of colony-stimulating factor. Significant increases in phagocytic macrophages (M phi) with Fc receptors for IgG2a and IgG2b immune complexes were additionally noted among the spleen cells in these mice. These M phi effectively inhibited Con A-induced lymphocyte proliferation, probably reflecting a 10-fold increase above normal controls in prostaglandin E to 47 ng/3 X 10(6) spleen cells/ml. To determine whether the suppressor M phi are immediate derivatives of splenic M-CFC, we tried to induce suppressor M phi by the injection of CP into mice depleted of bone marrow M-CFC by the earlier administration of the bone-seeking isotope, 89Sr. This procedure reduced M-CFC in the bone marrow to less than 1% of normal for more than 30 days. Monocytes in the blood fell to 5% of normal by day 10 and were 30% on day 30. Levels of resident peritoneal M phi showed relatively little change in this period. By contrast, splenic M-CFC increased to 20-fold higher than the cold 88Sr controls. CP-induced suppressor M phi activity, however, was sharply reduced in 89Sr marrow-depleted mice on day 10, despite the striking increase in M-CFC. There was a threefold increase in the number of phagocytic M phi binding IgG2a immune complexes, with no significant increase in IgG2b binding M phi. The kinetics of recovery of suppressor M phi activity showed that on days 20, 30, and 50 after 89Sr injection the activities reached 20%, 30%, and 70% of the cold control, respectively, and correlated with the recovery of significant levels of M-CFC in the bone marrow. Taken together, these observations suggest that splenic M-CFC are not an immediate source of PGE-suppressor M phi in vivo

  3. Ex vivo perfusion of human spleens maintains clearing and processing functions.

    Science.gov (United States)

    Buffet, Pierre A; Milon, Geneviève; Brousse, Valentine; Correas, Jean-Michel; Dousset, Bertrand; Couvelard, Anne; Kianmanesh, Reza; Farges, Olivier; Sauvanet, Alain; Paye, François; Ungeheuer, Marie-Noëlle; Ottone, Catherine; Khun, Huot; Fiette, Laurence; Guigon, Ghislaine; Huerre, Michel; Mercereau-Puijalon, Odile; David, Peter H

    2006-05-01

    The spleen plays a central role in the pathophysiology of several potentially severe diseases such as inherited red cell membrane disorders, hemolytic anemias, and malaria. Research on these diseases is hampered by ethical constraints that limit human spleen tissue explorations. We identified a surgical situation--left splenopancreatectomy for benign pancreas tumors--allowing spleen retrieval at no risk for patients. Ex vivo perfusion of retrieved intact spleens for 4 to 6 hours maintained a preserved parenchymal structure, vascular flow, and metabolic activity. Function preservation was assessed by testing the ability of isolated-perfused spleens to retain Plasmodium falciparum-infected erythrocytes preexposed to the antimalarial drug artesunate (Art-iRBCs). More than 95% of Art-iRBCs were cleared from the perfusate in 2 hours. At each transit through isolated-perfused spleens, parasite remnants were removed from 0.2% to 0.23% of Art-iRBCs, a proportion consistent with the 0.02% to 1% pitting rate previously established in artesunate-treated patients. Histologic analysis showed that more than 90% of Art-iRBCs were retained and processed in the red pulp, providing the first direct evidence of a zone-dependent parasite clearance by the human spleen. Human-specific physiologic or pathophysiologic mechanisms involving clearing or processing functions of the spleen can now be experimentally explored in a human tissue context.

  4. Thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism.

    Science.gov (United States)

    Duan, Ya-Qi; Liang, Ping

    2013-05-01

    Many studies have been conducted on splenic thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In this article, we review the evolution and current status of radiofrequency and microwave ablation in the treatment of spleen diseases. All publications from 1990 to 2011 on radiofrequency and microwave ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism were retrieved by searching PubMed. Thermal ablation in the spleen for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism can preserve part of the spleen and maintain splenic immunologic function. Thermal ablation for assisting hemostasis in partial splenectomy minimizes blood loss during operation. Thermal ablation for spleen trauma reduces the number of splenectomy and the amount of blood transfusion. Thermal ablation for splenic metastasis is minimally invasive and can be done under the guidance of an ultrasound, which helps shorten the recovery time. Thermal ablation for hypersplenism increases platelet (PLT) and white blood cell (WBC) counts and improves liver function. It also helps to maintain splenic immunologic function and even improves splenic immunologic function in the short-term. In conclusion, thermal ablative approaches are promising for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In order to improve therapeutic effects, directions for future studies may include standardized therapeutic indications, prolonged observation periods and enlarged sample sizes.

  5. Influence of apoptosis on liver and spleen resistance in dogs with visceral leishmaniosis.

    Science.gov (United States)

    Moreira, Pamela Rodrigues Reina; Franciscato, Douglas Augusto; Rossit, Sabrina Micelli; Munari, Danísio Prado; Vasconcelos, Rosemeri de Oliveira

    2016-01-01

    The aim of this study was to evaluate apoptosis and parasite load in the liver and spleen of dogs with visceral leishmaniosis (VL), using immunohistochemistry. Liver and spleen samples from 71 dogs with VL were used. The parasite load in the spleen and liver showed significant difference between organs in infected group (P=0.0219). The density of the parasite load in the spleen (median=2.4) was higher than liver (median=0.8). Immunodetection of apoptotic cells was predominant in lymphocytes and differ between the infected and control group in spleen (P=0.0307) and liver (P=0.0346). There was a significant correlation between apoptosis and parasite load (P = 0.0084; r=0.3104) only in the spleen of the infected group, where it was observed that, when increasing the number of apoptotic cells increases the parasitic load. It was concluded that the liver and spleen of infected dogs presented greater numbers of cells undergoing apoptosis (lymphocytes) than the control group, thus suggesting that this process may be contributing towards the survival of Leishmania in these organs, because lymphocyte in apoptosis did not have the ability to present and recognize the antigen, allowing the survival of the parasite.

  6. Induced Pluripotent Stem Cells from Nonhuman Primates.

    Science.gov (United States)

    Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

    2016-01-01

    Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

  7. Changing spleen size after blunt abdominal trauma

    International Nuclear Information System (INIS)

    Goodman, L.R.; Aprahamian, C.

    1989-01-01

    The authors studied the incidence and significance of splenic enlargement on serial CT after abdominal trauma. Spleen size and density in 44 trauma patients were studied with serial, contrast-enhanced Ct. In 58% of the patients, ≥ 10% enlargement of the spleen was seen on follow-up scans. Ten patients had >50% enlargement. In several, the initial density of the spleen was less than that of the liver. Spleen density returned to normal on subsequent scans. Correlations between splenic changes and clinical parameters (such as blood replacement, hypotension, and various trauma indexes) were weak. The author's study indicated that serial splenic enlargement was a physiologic return to normal after major trauma, not a pathologic condition requiring splenectomy

  8. Recurrent spleen enlargement during cyclic granulocyte-macrophage colony-stimulating factor therapy for myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Delmer, A.; Karmochkine, M.; Cadiou, M.; Gerhartz, H.; Zittoun, R.

    1990-01-01

    A 65-year-old woman with refractory anemia with excess of blasts received sequential courses of granulocyte-macrophage colony-stimulating factor therapy (GM-CSF) and low-dose cytosine arabinoside. Each course of GM-CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111-indium chloride scanning suggested a myeloid metaplasia of the spleen. This observation suggests that in some patients the granulopoietic response to the myeloid growth factor stimulation may be predominant in the spleen

  9. Scintigraphy of liver and spleen in vinyl chloride workers

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H J; San Luis, T Jr; Lange, C E; Thelen, M; Veltman, G; Winkler, C [Bonn Univ. (Germany, F.R.). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Bonn Univ. (Germany, F.R.). Klinik und Poliklinik der Haut- und Geschlechtskrankheiten; Bonn Univ. (Germany, F.R.). Radiologische Klinik)

    1977-10-01

    In 152 VC-exposed workers of whom 124 were employed in the PVC-production and 28 in VC-processing plants, liver and spleen imaging was performed using sup(99m)Tc-sulphur colloid and /sup 197/Hg-BMHP. In 101 (= 81%) of the 124 workers of the PVC-production plant and in 18 (= 64%) workers of PVC-processing factories pathological liver and spleen scintigrams were found. The most frequent pathological change in the scintigraphic image was an increase in splenic colloid accumulation, when compared with the liver uptake. Three angiosarcomas of the liver were detected through circumscribed defects of colloid accumulation. Sequential liver scintigraphy was done in 15 cases. In 7 patients with esophageal varices, considerable decrease in portal venous blood flow was demonstrated. - As a result of our investigations it can be stated that scintigraphically detectable changes are sensitive indicators of VC-induced lesions of the liver including liver fibrosis, portal hypertension and angiosarcoma.

  10. Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice

    Directory of Open Access Journals (Sweden)

    Shanzheng Lu

    2016-10-01

    Full Text Available Abstract Background The endometrial regenerative cell (ERC is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4–induced acute liver injury (ALI. Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT and aspartate aminotransferase (AST activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury

  11. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Directory of Open Access Journals (Sweden)

    Tobias Eggert

    Full Text Available Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL, while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  12. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Science.gov (United States)

    Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

    2014-01-01

    Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  13. Immune response to UV-induced tumors: mediation of progressor tumor rejection by natural killer cells

    International Nuclear Information System (INIS)

    Streeter, P.R.; Fortner, G.W.

    1986-01-01

    Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic animals. In the present study, the authors compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either regressor or progressor UV-tumors. The results of this comparison implicated tumor-specific cytolytic T (Tc) lymphocytes in rejection of regressor UV-tumors, and revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific Tc cells even as the tumors rejected. Following in vitro resensitization of spleen cells from either regressor or progressor tumor immune animals, the authors found NK-like lymphocytes with anti-tumor activity. As the authors had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, the authors examined lymphocytes from the local tumor environment during the course of progressor tumor rejection for this activity. This analysis revealed NK lymphocytes exhibiting significant levels of cytolytic activity against UV-tumors. These results implicate NK cells as potential effector cells in the rejection of progressor UV-tumors by immune animals, and suggests that these cells may be regulated by T lymphocytes

  14. Radiation-induced cell damage

    International Nuclear Information System (INIS)

    Felix, W.D.; Schneiderman, M.H.

    1976-01-01

    The addition of irradiated crystals of galactose to Chinese hamster ovary cells resulted in mitotic delay, whereas exposure to nonirradiated crystals resulted in no detectable delay. The inference from this preliminary data is that free radicals or other transient irradiation products have reacted with external cellular components

  15. TWEAK induces liver progenitor cell proliferation

    Science.gov (United States)

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

    2005-01-01

    Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  16. Induced pluripotent stem cells for regenerative medicine.

    Science.gov (United States)

    Hirschi, Karen K; Li, Song; Roy, Krishnendu

    2014-07-11

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.

  17. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    Tease, C.

    1989-01-01

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  18. Resveratrol induces mitochondrial biogenesis in endothelial cells.

    Science.gov (United States)

    Csiszar, Anna; Labinskyy, Nazar; Pinto, John T; Ballabh, Praveen; Zhang, Hanrui; Losonczy, Gyorgy; Pearson, Kevin; de Cabo, Rafael; Pacher, Pal; Zhang, Cuihua; Ungvari, Zoltan

    2009-07-01

    Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.

  19. Obesity-related chronic kidney disease is associated with spleen-derived IL-10.

    Science.gov (United States)

    Gotoh, Koro; Inoue, Megumi; Masaki, Takayuki; Chiba, Seiichi; Shiraishi, Kentaro; Shimasaki, Takanobu; Matsuoka, Kazue; Ando, Hisae; Fujiwara, Kansuke; Fukunaga, Naoya; Aoki, Kohei; Nawata, Tomoko; Katsuragi, Isao; Kakuma, Tetsuya; Seike, Masataka; Yoshimatsu, Hironobu

    2013-05-01

    Obesity is associated with systemic low-grade inflammation and is a risk factor for chronic kidney disease (CKD), but the molecular mechanism remains uncertain. We noticed spleen-derived interleukin (IL)-10 because it is observed that obesity reduces several cytokines in the spleen. We examined whether spleen-derived IL-10 regulates CKD caused by a high-fat diet (HF)-induced obesity as follows: (i) male mice were fed with HF (60% fat) during 8 weeks and IL-10 induction from the spleen was examined, (ii) glomerular hypertrophy, fibrosis, inflammatory responses in the kidney and systolic blood pressure (SBP) were evaluated in splenectomy (SPX)-treated mice fed HF, (iii) exogenous IL-10 was systemically administered to HF-induced obese mice and the alteration of obesity-induced pathogenesis caused by IL-10 treatment was assessed. (iv) IL-10 knockout (IL-10KO) mice were treated with SPX and glomerular hypertrophy, fibrosis and the inflammatory condition in the kidney and SBP were also investigated. Obesity decreased serum levels of only IL-10, an anti-inflammatory cytokine even though pro- and anti-inflammatory cytokine expression in the spleen was significantly lower in the obese group. SPX aggravated HF-induced inflammatory responses in the kidney and hypertension. These HF-induced alterations were inhibited by systemically administered IL-10. Moreover, SPX had little effect on inflammatory responses and SBP in the kidney of IL-10KO mice. We suggest that obesity reduces IL-10 induction from the spleen, and spleen-derived IL-10 may protect against the development of CKD induced by obesity.

  20. Induced repair and mutagenesis in animal cells

    International Nuclear Information System (INIS)

    Takimoto, Koichi

    1981-01-01

    Induced repair and mutagenesis of animal cells against UV were studied in contrast with SOS repair of E. coli primarily by the use of viruses. Since UV-enhanced reactivation is a phenomenon similar to UV-reactivation (mutagenesis) and the presence of lesion bypass synthsis has been suggested, UV-enhanced reactivation has several common aspects with SOS reactivation of E. coli. However, correlation is not necessarily noted between increase in the viral survival rate and mutagenesis, nor do protease blockers exert any effect. Therefore, SOS repair of E. coli may have different mechansms from induced repair and mutagenesis in animal cells. (Ueda, J.)

  1. Somatostatin receptor expression in the human spleen - Answer to an enigma by ex-vivo and in-vitro autoradiography after 177Lu-DOTA-octreotate administration

    International Nuclear Information System (INIS)

    Melis, M.; Swart, J. de; Groen, H.C.; Konijnenberg, M.W.; Van der Graaf, L.M.; Kaemmerer, D.; Kulkami, H.R.; Baum, R.P.; Lupp, A.; Saenger, J.; Jong, M. de

    2015-01-01

    Full text of publication follows. Aim: radiolabelled somatostatin analogues are being used for diagnostic and therapeutic (PRRT) purposes in patients with somatostatin receptor (SSTR) expressing tumours. During PRRT a significant spleen uptake may lead to radiation doses of > 20 Gy. Yet, the threshold dose for spleen radiation induced toxicity is currently unknown. Based on previous 68 Ga-DOTATOC PET/CT studies, demonstrating higher uptake in spleen than in splenosis, white pulp (WP) localization of radioactivity was suggested. This hypothesis was investigated in the current pilot study using the longer lived 177 Lu-DOTA-octreotate. Methods: a patient diagnosed with neuroendocrine neoplasm of the pancreatic tail (SUV max on 68 Ga-DOTATOC PET/CT 100.4) with liver metastasis (SUV 47.3, normal liver SUV 12.5) and uptake in the spleen (SUV 41.0) received 1 GBq 177 Lu-DOTA-octreotate. 2 h after administration whole-body planar scintigraphy and SPECT/CT of the upper abdomen was performed, followed by laparoscopic resection of the pancreatic tumour and splenectomy the next day. After spleen transport from Bad Berka to Rotterdam ex-vivo micro-SPECT of the removed spleen was acquired for 73 min using 2.5 mm diameter pinholes. Spleen fragments (∼10 * 10 * 5 mm) were either snap-frozen in liquid nitrogen or fixed in 10% formalin and paraffin embedded. Ex-vivo autoradiography of 10 μm cryo-sections was performed and serial sections were used for 111 In-DOTA-octreotate in-vitro autoradiography after decay of 177 Lu. FFPE sections were used for HE- and immunostaining for SSTR2A and cell subsets CD4 (Th-cell), CD8 (Ts-cell), CD20 (B-cell) and CD68 (macrophage). Results: 177 Lu-DOTA-octreotate scintigraphy and SPECT/CT demonstrated high uptake in the pancreatic tumor, hepatic metastasis and homogeneously in the normal spleen. High resolution micro-SPECT imaging of the isolated spleen also revealed a relatively homogeneous uptake (calculated rest activity 60 MBq 177 Lu). The

  2. Induced DNA repair pathway in mammalian cells

    International Nuclear Information System (INIS)

    Overberg, R.

    1985-01-01

    The survival of cultured rat kangaroo cells (PtK-2) and human xeroderma pigmentosum cells incubated with 5 μM cycloheximide subsequent to ultraviolet irradiation is lower than that of cells incubated without cycloheximide. The drop in survival is considerably larger than that produced by incubation of unirradiated cells with cycloheximide. The phenomenon was also observed when PtK-2 cells were incubated with emetine, another protein synthesis inhibitor, or with 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole, a RNA synthesis inhibitor. PtK cells which received a preliminary UV treatment followed by an incubation period without cycloheximide and then a second irradiation and 24 hour incubation with cycloheximide, survived the effects of the second irradiation better than cells which were incubated in the presence of cycloheximide after the first and second UV irradiation. The application of cycloheximide for 24 hours after UV irradiation of PtK cells resulted in one-half as many 6-thioguanine resistant cells as compared to the number of 6-thioguanine resistant cells found when cycloheximide was not used. These experiments indicate that a UV-inducible cycloheximide-sensitive DNA repair pathway is present in PtK and xeroderma pigmentosum cells, which is error-prone in PtK cells

  3. Spleen-preserving distal pancreatectomy in trauma.

    Science.gov (United States)

    Schellenberg, Morgan; Inaba, Kenji; Cheng, Vincent; Bardes, James M; Lam, Lydia; Benjamin, Elizabeth; Matsushima, Kazuhide; Demetriades, Demetrios

    2018-01-01

    Traumatic injuries to the distal pancreas are infrequent. Universally accepted recommendations about the need for routine splenectomy with distal pancreatectomy do not exist. The aims of this study were to compare outcomes after distal pancreatectomy and splenectomy versus spleen-preserving distal pancreatectomy, and to define the appropriate patient population for splenic preservation. All patients who underwent distal pancreatectomy (January 1, 2007, to December 31, 2014) were identified from the National Trauma Data Bank. Patients with concomitant splenic injury and those who underwent partial splenectomy were excluded. Demographics, clinical data, procedures, and outcomes were collected. Study groups were defined by surgical procedure: distal pancreatectomy and splenectomy versus spleen-preserving distal pancreatectomy. Baseline characteristics between groups were compared with univariate analysis. Multivariate analysis was performed with logistic and linear regression to examine differences in outcomes. Over the 8-year study period, 2,223 patients underwent distal pancreatectomy. After excluding 1,381 patients with concomitant splenic injury (62%) and 8 (pancreatectomy and splenectomy, those who underwent spleen-preserving distal pancreatectomy were younger (p pancreatectomy (p = 0.017). Complications, mortality, and intensive care unit LOS were not significantly different. In young patients after blunt trauma who are not severely injured, a spleen-preserving distal pancreatectomy should be considered to allow for conservation of splenic function and a shorter hospital LOS. In all other patients, the surgeon should not hesitate to remove the spleen with the distal pancreas. Therapy, level IV.

  4. Novel contrast agent for liver and spleen

    International Nuclear Information System (INIS)

    Seltzer, S.E.; Blau, M.; Adams, D.F.; Janoff, A.; Minchey, S.

    1991-01-01

    This paper determines whether the biodistribution and imaging characteristics of a liposome-encapsulated contrast agent, iotrolan-carrying interdigitation fusion (IF) vesicles, were acceptable for a liver-spleen CT contrast agent. IF vesicles with iotrolan in their aqueous phase were prepared by fusing small unilamellar liposomes into larger vesicles. The iodine-to-lipid ratio was 4.7. Biodistribution was measured with I-125 iotrolan-labeled IF vesicles in rats. CT imaging (Somatom Plus, Siemens Medical Systems) was performed in dogs. At the lowest dose (10 mg of iodine and 2.1 mg of lipid per kilogram) 72% of the ID was in the liver, 5% in spleen, and 1% in lungs at 1 hour. At the highest dose, (1,000 mg of iodine and 212 mg of lipid per kilogram), liver values were 68% ID, while spleen rose to 18%, lung 5%. Liver and spleen values stayed at peak for 24 hours then fell; the half-life was 6 days. In dogs, liver and spleen enhancement at 1 hour averaged 652 and 256 HU above baseline per gram of iodine per kilogram, respectively

  5. Trophoblast lineage cells derived from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  6. Trophoblast lineage cells derived from human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard

    2013-01-01

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

  7. Cell cycle arrest induced by radiation

    International Nuclear Information System (INIS)

    Okaichi, Yasuo; Matsumoto, Hideki; Ohnishi, Takeo

    1994-01-01

    It is known that various chemical reactions, such as cell cycle arrest, DNA repair and cell killing, can occur within the cells when exposed to ionizing radiation and ultraviolet radiation. Thus protein dynamics involved in such chemical reactions has received considerable attention. In this article, cell cycle regulation is first discussed in terms of the G2/M-phase and the G1/S-phase. Then, radiation-induced cell cycle arrest is reviewed. Cell cycle regulation mechanism involved in the G2 arrest, which is well known to occur when exposed to radiation, has recently been investigated using yeasts. In addition, recent study has yielded a noticeable finding that the G1 arrest can occur with intracellular accumulation of p53 product following ionization radiation. p53 is also shown to play an extremely important role in both DNA repair and cell killing due to DNA damage. Studies on the role of genes in protein groups induced by radiation will hold promise for the elucidation of cell cycle mechanism. (N.K.) 57 refs

  8. Spleen size changes in children with homozygous β-thalassaemia in relation to blood transfusion

    International Nuclear Information System (INIS)

    Karpathios, Th.; Antypas, A.; Dimitriou, P.; Nicolaidou, P.; Fretzayas, A.; Thomaidis, Th.; Matsaniotis, N.

    1982-01-01

    18 thalassaemic children, aged 3.5 to 13 years comprise our clinical material. In 14 of them, clinically elicited spleen markings, haematocrit, blood platelet count and red cell morphology were studied daily for a whole period between 2 transfusions. In 10 patients considerable changes in spleen size were noticed. According to our clinical observations the spleen size starts decreasing 1 to 3 d after blood transfusion up to the 10th posttransfusion day fluctuating thereafter to reach its maximum size again prior to the next blood transfusion. The decrease of spleen size was followed by an increase of haematocrit and blood platelet count and vice versa. 4 additional children were studied clinically only twice: prior to and 7 to 10 d after blood transfusion. A definite decrease of the spleen size following blood transfusion was observed. Spleen and liver sup(99m)Tc-sulfur colloid uptake was studied in 10 of the above children prior to and 7 to 10 d after blood transfusion. Statistically significant post-transfusion increase of the spleen uptake was demonstrated. Our findings suggest that (a) splenic size is relevant to blood volume sequestrated int this organ, (b) splenic radioactive uptake increases with its post-transfusion reductin in size. (author)

  9. Function of the replanted spleen in dogs

    International Nuclear Information System (INIS)

    Velcek, F.T.; Kugaczewski, J.T.; Jongco, B.; Shaftan, G.W.; Rao, P.S.; Schiffman, G.; Kottmeier, P.K.

    1982-01-01

    The function of replanted splenic fragments was studied by comparing three groups of five dogs each, one group with intact spleens; one, post-splenectomy; and one with splenic replantation. Fifteen fragments were implanted into the omentum. Howell-Jolly bodies appeared after splenectomy but cleared in the replanted group after several months. 125 I-tagged attenuated pneumococcal clearance studies showed a significant difference between control and replanted group compared with the splenectomized group. The increase of pneumococcal antibody titers after vaccination differed significantly between the splenectomized and the replanted group. All replanted fragments were viable and showed growth over a 2-year period. These studies demonstrate that omental replantation of the canine spleen leads to the maintenance of certain functional splenic parameters comparable to the normal spleen which are significantly different from the splenectomized animal

  10. Function of the replanted spleen in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Velcek, F.T.; Kugaczewski, J.T.; Jongco, B.; Shaftan, G.W.; Rao, P.S.; Schiffman, G.; Kottmeier, P.K.

    1982-06-01

    The function of replanted splenic fragments was studied by comparing three groups of five dogs each, one group with intact spleens; one, post-splenectomy; and one with splenic replantation. Fifteen fragments were implanted into the omentum. Howell-Jolly bodies appeared after splenectomy but cleared in the replanted group after several months. /sup 125/I-tagged attenuated pneumococcal clearance studies showed a significant difference between control and replanted group compared with the splenectomized group. The increase of pneumococcal antibody titers after vaccination differed significantly between the splenectomized and the replanted group. All replanted fragments were viable and showed growth over a 2-year period. These studies demonstrate that omental replantation of the canine spleen leads to the maintenance of certain functional splenic parameters comparable to the normal spleen which are significantly different from the splenectomized animal.

  11. Blunt trauma to the spleen: ultrasonographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Doody, O. [Department of Radiology, Tallaght Hospital, Dublin (Ireland); Lyburn, D. [Department of Radiology, Cheltenham General Hospital (United Kingdom); Geoghegan, T. [Department of Radiology, Tallaght Hospital, Dublin (Ireland); Govender, P. [Department of Radiology, Tallaght Hospital, Dublin (Ireland); Monk, P.M. [Department of Radiology, Vancouver Hospital (Canada); Torreggiani, W.C. [Department of Radiology, Tallaght Hospital, Dublin (Ireland)]. E-mail: william.torreggiani@amnch.ie

    2005-09-01

    The spleen is the most frequently injured organ in adults who sustain blunt abdominal trauma. Splenic trauma accounts for approximately 25% to 30% of all intra-abdominal injuries. The management of splenic injury has undergone rapid change over the last decade, with increasing emphasis on splenic salvage and non-operative management. Identifying the presence and degree of splenic injury is critical in triaging the management of patients. Imaging is integral in the identification of splenic injuries, both at the time of injury and during follow-up. Although CT remains the gold standard in blunt abdominal trauma, US continues to play an important role in assessing the traumatized spleen. This pictorial review illustrates the various ultrasonographic appearances of the traumatized spleen. Correlation with other imaging is presented and complications that occur during follow-up are described.

  12. Postnatal development of the spleen in Didelphis virginiana.

    Science.gov (United States)

    Cutts, J H; Krause, W J

    1982-01-01

    The postnatal development of the spleen has been examined in 85 opossums ranging in age from newborn to adult. At birth the spleen consists of a well vascularized mass of mesenchymal tissue and lacks lymphatic tissue or any evidence of haemopoietic activity. Haemopoiesis is evident at seven days, increases to a maximum at about two to three weeks and thereafter gradually declines. Although production of granulocytes has disappeared by 60 days postnatum, a small degree of erythropoiesis and megakaryocyte formation continues throughout life. Lymphatic tissue appears by the third week, but germinal centres do not appear until after weaning. A feature of the spleen during the first three to four days is the presence of a population of primitive 'blast' cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 21 Fig. 22 Fig. 23 Fig. 24 PMID:7153176

  13. Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice

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    Altintas Mehmet M

    2012-02-01

    Full Text Available Abstract Background Mast cells are implicated in the pathogenesis of obesity and insulin resistance. Here, we explored the effects of leptin deficiency-induced obesity on the density of mast cells in metabolic (abdominal fat depots, skeletal muscle, and liver and lymphatic (abdominal lymph nodes, spleen, and thymus organs. Fourteen-week-old male leptin-deficient ob/ob mice and their controls fed a standard chow were studied. Tissue sections were stained with toluidine blue to determine the density of mast cells. CD117/c-kit protein expression analysis was also carried out. Furthermore, mast cells containing immunoreactive tumor necrosis factor-α (TNF-α, a proinflammatory cytokine involved in obesity-linked insulin resistance, were identified by immunostaining. Results ob/ob mice demonstrated adiposity and insulin resistance. In abdominal fat depots, mast cells were distributed differentially. While most prevalent in subcutaneous fat in controls, mast cells were most abundant in epididymal fat in ob/ob mice. Leptin deficiency-induced obesity was accompanied by a 20-fold increase in the density of mast cells in epididymal fat, but a 13-fold decrease in subcutaneous fat. This finding was confirmed by CD117/c-kit protein expression analysis. Furthermore, we found that a subset of mast cells in epididymal and subcutaneous fat were immunoreactive for TNF-α. The proportion of mast cells immunoreactive for TNF-α was higher in epididymal than in subcutaneous fat in both ob/ob and control mice. Mast cells were also distributed differentially in retroperitoneal, mesenteric, and inguinal lymph nodes. In both ob/ob mice and lean controls, mast cells were more prevalent in retroperitoneal than in mesenteric and inguinal lymph nodes. Leptin deficiency-induced obesity was accompanied by increased mast cell density in all lymph node stations examined. No significant difference in the density of mast cells in skeletal muscle, liver, spleen, and thymus was

  14. Erythroblast differentiation at spleen in Q137E mutant ribosomal protein S19 gene knock-in C57BL/6J mice.

    Science.gov (United States)

    Yamanegi, Koji; Yamada, Naoko; Nakasho, Keiji; Nishiura, Hiroshi

    2018-01-01

    We recently found that erythroblast-like cells derived from human leukaemia K562 cells express C5a receptor (C5aR) and produce its antagonistic and agonistic ligand ribosomal protein S19 (RP S19) polymer, which is cross-linked between K122 and Q137 by tissue transglutaminases. RP S19 polymer binds to the reciprocal C5aRs on erythroblast-like cells and macrophage-like cells derived from human monocytic THP-1 cells and promotes differentiation into reticulocyte-like cells through enucleation in vitro. To examine the roles of RP S19 polymer in mouse erythropoiesis, we prepared Q137E mutant RP S19 gene knock-in C57BL/6J mice. In contrast to wild-type mice, erythroblast numbers at the preliminary stage (CD71 high /TER119 low ) in spleen based on transferrin receptor (CD71) and glycophorin A (TER119) values and erythrocyte numbers in orbital artery bloods were not largely changed in knock-in mice. Conversely, erythroblast numbers at the early stage (CD71 high /TER119 high ) were significantly decreased in spleen by knock-in mice. The reduction of early erythroblast numbers in spleen was enhanced by the phenylhydrazine-induced pernicious anemia model knock-in mice and was rescued by a functional analogue of RP S19 dimer S-tagged C5a/RP S19. These data indicated that RP S19 polymer plays the roles in the early erythroblast differentiation of C57BL/6J mouse spleen. Copyright © 2017 Elsevier GmbH. All rights reserved.

  15. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  16. Laparoscopic Splenectomy in Patients With Spleen Injuries.

    Science.gov (United States)

    Ermolov, Aleksander S; Tlibekova, Margarita A; Yartsev, Peter A; Guliaev, Andrey A; Rogal, Mikhail M; Samsonov, Vladimir T; Levitsky, Vladislav D; Chernysh, Oleg A

    2015-12-01

    Spleen injury appears in 10% to 30% of abdominal trauma patients. Mortality among the patients in the last 20 years remains high (6% to 7%) and shows no tendency to decline. Nowadays nonoperative management is widely accepted management of patients with low-grade spleen injury, whereas management of patients with high-grade spleen injury (III and higher) is not so obvious. There are 3 methods exist in treatment of such patients: conservative (with or without angioembolization), spleen-preserving operations, and splenectomy. Today laparoscopic splenectomy is not a widely used operation and only few studies reported about successful use of laparoscopic splenectomy in patients with spleen injury.The aim of the study was to determine indications and contraindications for laparoscopic splenectomy in abdominal trauma patients and to analyze results of the operations. The study involved 42 patients with spleen injury grade III who were admitted in our institute in the years of 2010 to 2014. The patients were divided in 2 groups. Laparoscopic splenectomy was performed in 23 patients (group I) and "traditional" splenectomy was carried out in 19 patients (group II). There was no difference in the demographic data and trauma severity between the 2 groups. Noninvasive investigations, such as laboratory investigations, serial abdominal ultrasound examinations, x-ray in multiple views, and computed tomography had been performed before the decision about necessity of an operation was made. Patients after laparoscopic operations had better recovering conditions compared with patients with the same injury after "traditional" splenectomy. Neither surgery-related complications nor mortalities were registered in both groups. Laparoscopic splenectomy was more time-consuming operation than "traditional" splenectomy. We suggest that as experience of laparoscopic splenectomy is gained the operation time will be reduced. Laparoscopic splenectomy is a safe feasible operation in patients

  17. Expression of tyrosine hydroxylase in CD4+ T cells contributes to alleviation of Th17/Treg imbalance in collagen-induced arthritis.

    Science.gov (United States)

    Wang, Xiao-Qin; Liu, Yan; Cai, Huan-Huan; Peng, Yu-Ping; Qiu, Yi-Hua

    2016-12-01

    Tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of catecholamines, is expressed in T lymphocytes. However, the role of T cell-expressed TH in rheumatoid arthritis (RA) is less clear. Herein, we aimed to show the contribution of TH expression by CD4 + T cells to alleviation of helper T (Th)17/regulatory T (Treg) imbalance in collagen-induced arthritis (CIA), a mouse model of RA. CIA was prepared by intradermal injection of collagen type II (CII) at tail base of DBA1/J mice. Expression of TH in the spleen and the ankle joints was measured by real-time polymerase chain reaction and Western blot analysis. Percentages of TH-expressing Th17 and Treg cells in splenic CD4 + T cells were determined by flow cytometry. Overexpression and knockdown of TH gene in CD4 + T cells were taken to evaluate effects of TH on Th17 and Treg cells in CIA. TH expression was upregulated in both the inflamed tissues (spleen and ankle joints) and the CD4 + T cells of CIA mice. In splenic CD4 + T cells, the cells expressing TH were increased during CIA. These cells that expressed more TH in CIA were mainly Th17 cells rather than Treg cells. TH gene overexpression in CD4 + T cells from CIA mice reduced Th17 cell percentage as well as Th17-related transcription factor and cytokine expression and secretion, whereas TH gene knockdown enhanced the Th17 cell activity. In contrast, TH gene overexpression increased Treg-related cytokine expression and secretion in CD4 + T cells of CIA mice, while TH gene knockdown decreased the Treg cell changes. Collectively, these findings show that CIA induces TH expression in CD4 + T cells, particularly in Th17 cells, and suggest that the increased TH expression during CIA represents an anti-inflammatory mechanism.

  18. Menstruum induces changes in mesothelial cell morphology.

    Science.gov (United States)

    Koks, C A; Demir Weusten, A Y; Groothuis, P G; Dunselman, G A; de Goeij, A F; Evers, J L

    2000-01-01

    In previous studies, we have shown that menstrual endometrium preferentially adheres to the subepithelial lining of the peritoneum. It remains to be elucidated, however, whether this damage is preexisting or inflicted by the menstrual tissue itself. We hypothesized that the menstrual tissue itself damages the peritoneum. To investigate this, the viability of menstrual endometrial tissue in peritoneal fluid (PF) was evaluated and the morphologic changes in the mesothelial cells were studied by in vitro cocultures of menstruum with mesothelial cell monolayers. Menstruum was collected with a menstrual cup. Endometrial tissue was isolated from the menstruum, resuspended in culture medium or in the cell-free fraction of PF and cultured for 24, 48 or 72 h. A 3(4, 5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to obtain a relative measure of viable adhered endometrial cells. Mesothelial cells isolated from human omental tissue were cultured on Matrigel or uncoated plastic. At confluence, overnight cocultures were performed and scanning electron microscopy was used to evaluate the morphologic changes. The viability of endometrial fragments was 84% (n = 36, p Menstrual endometrial fragments or menstrual serum added to and cocultured with mesothelial cells induced severe morphologic alterations of the latter, including retraction, shrinking and gap formation. Similar morphologic changes were observed when mesothelial cells were cocultured with menstrual endometrial fragments in PF or in culture inserts. Incubation with conditioned medium from cultured menstrual endometrium induced similar but less pronounced changes in morphology. In conclusion, menstrual endometrial fragments remain viable in PF in vitro for at least 72 h. Antegradely shed menstruum induces changes in mesothelial cell morphology, including retraction and shrinking with exposure of the underlying surface. These findings suggest that menstruum is harmful to the peritoneal

  19. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells

    Science.gov (United States)

    Rezende, Rafael M.; Oliveira, Rafael P.; Medeiros, Samara R.; Gomes-Santos, Ana C.; Alves, Andrea C.; Loli, Flávia G.; Guimarães, Mauro A.F.; Amaral, Sylvia S.; da Cunha, André P.; Weiner, Howard L.; Azevedo, Vasco; Miyoshi, Anderson; Faria, Ana M.C.

    2013-01-01

    Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-β - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice. PMID:22939403

  20. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Directory of Open Access Journals (Sweden)

    Tongfang Tang

    Full Text Available BACKGROUND: Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD through alternation of liver innate immune response. AIMS: The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. METHODS: Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. RESULTS: High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4 expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. CONCLUSION: High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  1. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Science.gov (United States)

    Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

    2013-01-01

    Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  2. Curcumin induces autophagic cell death in Spodoptera frugiperda cells.

    Science.gov (United States)

    Veeran, Sethuraman; Shu, Benshui; Cui, Gaofeng; Fu, Shengjiao; Zhong, Guohua

    2017-06-01

    The increasing interest in the role of autophagy (type II cell death) in the regulation of insect toxicology has propelled study of investigating autophagic cell death pathways. Turmeric, the rhizome of the herb Curcuma longa (Mañjaḷ in Tamil, India and Jiānghuáng in Chinese) have been traditionally used for the pest control either alone or combination with other botanical pesticides. However, the mechanisms by which Curcuma longa or curcumin exerts cytotoxicity in pests are not well understood. In this study, we investigated the potency of Curcuma longa (curcumin) as a natural pesticide employing Sf9 insect line. Autophagy induction effect of curcumin on Spodoptera frugiperda (Sf9) cells was investigated using various techniques including cell proliferation assay, morphology analysis with inverted phase contrast microscope and Transmission Electron Microscope (TEM) analysis. Autophagy was evaluated using the fluorescent dye monodansylcadaverine (MDC). Cell death measurement was examined using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) within the concentrations of 5-15μg/mL. Curcumin inhibited the growth of the Sf9 cells and induced autophagic cell death in a time and dose dependent manner. Staining the cells with MDC showed the presence of autophagic vacuoles while increased in a dose and time dependent manner. At the ultrastructural level transmission electron microscopy, cells revealed massive autophagy vacuole accumulation and absence of chromatin condensation. Protein expression levels of ATG8-I and ATG8-II, well-established markers of autophagy related protein were elevated in a time dependent manner after curcumin treatment. The present study proves that curcumin induces autophagic cell death in Sf9 insect cell line and this is the first report of cytotoxic effect of curcumin in insect cells and that will be utilized as natural pesticides in future. Copyright © 2017. Published by Elsevier Inc.

  3. Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth.

    Science.gov (United States)

    Hojman, Pernille; Dethlefsen, Christine; Brandt, Claus; Hansen, Jakob; Pedersen, Line; Pedersen, Bente Klarlund

    2011-09-01

    Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.

  4. Paraquat-induced radiosensitization of mammalian cells

    International Nuclear Information System (INIS)

    Miller, R.C.; Fujikura, Toshio; Hiraoka, Toshio; Tenou, Hiromi.

    1983-06-01

    The herbicide, paraquat (methyl viologen, 1-1' dimethy1-4, 4'-bipyridinium dichloride), stimulates the production of superoxide anion (O 2 sup(-.)) in aerobic cells and therefore mimics some effects of ionizing radiation. In addition, concentrations of cellular glutathione are reduced by reaction with O 2 sup(-.). It is reported here that paraquat, toxic in its own right to aerobic cells, acts as a radiosensitizer when cells are exposed to nontoxic concentrations of the drug prior to and during irradiation. The radiomimetic effect of paraquat, alone and in combination with X-rays, was examined. Paraquat affects aerated cells (hamster lung V79 cells) in a dose-dependent manner. Doses in excess of 1 mM for two hours cause significant cell killing. In combination with radiation, sublethal doses of paraquat, given for two hours prior to irradiation, enhance the lethal effects of radiation. However, if cells are exposed to the same concentration of paraquat following irradiation, no additional lethal effect is observed. Paraquat is a useful tool to study the effects of O 2 sup(-.) and may lead to better understanding of the mechanisms of radiation-induced energy deposition in cells. (author)

  5. Sickle cell-induced ischemic colitis.

    Science.gov (United States)

    Stewart, Camille L; Ménard, Geraldine E

    2009-07-01

    Sickle cell-induced ischemic colitis is a rare yet potentially fatal complication of sickle cell anemia. Frequent pain crises with heavy analgesia may obscure and prolong this important diagnosis. Our patient was a 29-year-old female with sickle cell disease who was admitted with left lower quadrant abdominal pain. A diagnostic workup, including chemistries, complete blood count, blood cultures, chest x-ray, computerized tomography scanning, and colonoscopy, was performed to identify the etiology of her symptoms. This case highlights the importance of differentiating simple pain crisis from more serious and life-threatening ischemic bowel. A review of the literature compares this case to others reported and gives a method for diagnosing and treating this complication of sickle cell disease.

  6. Ionizing radiation-induced cell death

    International Nuclear Information System (INIS)

    Szumiel, I.

    1994-01-01

    Selected aspects of radiation-induced cell death, connected with signal transduction pathways are reviewed. Cell death is defined as insufficiency of the cellular signal transducing system to maintain the cell's physiological functions. The insufficiency may be due to impaired signal reception and/or transduction, lack or erroneous transcription activation, and eventual cellular ''misexpression'' of the signal. The molecular basis of this insufficiency would be damage to genomic (but also other cellular) structures and closing of specific signalling pathways or opening of others (like those leading to apoptosis). I describe experimental data that suggest an important role of RAS/NFI and p53/p105 Rb proteins in cell cycle control-coupled responses to DNA damage. (Author)

  7. Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells.

    Science.gov (United States)

    Tachikawa, Saoko; Nishimura, Toshinobu; Nakauchi, Hiromitsu; Ohnuma, Kiyoshi

    2017-10-01

    Thalidomide, which was formerly available commercially to control the symptoms of morning sickness, is a strong teratogen that causes fetal abnormalities. However, the mechanism of thalidomide teratogenicity is not fully understood; thalidomide toxicity is not apparent in rodents, and the use of human embryos is ethically and technically untenable. In this study, we designed an experimental system featuring human-induced pluripotent stem cells (hiPSCs) to investigate the effects of thalidomide. These cells exhibit the same characteristics as those of epiblasts originating from implanted fertilized ova, which give rise to the fetus. Therefore, theoretically, thalidomide exposure during hiPSC differentiation is equivalent to that in the human fetus. We examined the effects of thalidomide on undifferentiated hiPSCs and early-differentiated hiPSCs cultured in media containing bone morphogenetic protein-4, which correspond, respectively, to epiblast (future fetus) and trophoblast (future extra-embryonic tissue). We found that only the number of undifferentiated cells was reduced. In undifferentiated cells, application of thalidomide increased the number of apoptotic and dead cells at day 2 but not day 4. Application of thalidomide did not affect the cell cycle. Furthermore, immunostaining and flow cytometric analysis revealed that thalidomide exposure had no effect on the expression of specific markers of undifferentiated and early trophectodermal differentiated cells. These results suggest that the effect of thalidomide was successfully detected in our experimental system and that thalidomide eliminated a subpopulation of undifferentiated hiPSCs. This study may help to elucidate the mechanisms underlying thalidomide teratogenicity and reveal potential strategies for safely prescribing this drug to pregnant women.

  8. Inducible cell death in plant immunity

    DEFF Research Database (Denmark)

    Hofius, Daniel; Tsitsigiannis, Dimitrios I; Jones, Jonathan D G

    2006-01-01

    Programmed cell death (PCD) occurs during vegetative and reproductive plant growth, as typified by autumnal leaf senescence and the terminal differentiation of the endosperm of cereals which provide our major source of food. PCD also occurs in response to environmental stress and pathogen attack......, and these inducible PCD forms are intensively studied due their experimental tractability. In general, evidence exists for plant cell death pathways which have similarities to the apoptotic, autophagic and necrotic forms described in yeast and metazoans. Recent research aiming to understand these pathways...

  9. Induced pluripotent stem cells for retinal degenerative diseases: a ...

    Indian Academy of Sciences (India)

    2009-12-31

    Dec 31, 2009 ... anisms of these diseases is still very limited and no radical drugs are available. Induced .... Induced pluripotent stem cells are ES-like pluripotent cells capable of .... lation to test whether immunorejection with the latter is in-.

  10. Toxoplasma gondii vs ionizing radiation: cell and humoral immunity in spleen and gut of isogenic mice immunized with {sup 60}Co irradiated tachyzoites; Toxoplasma gondii vs radiacao ionizante: imunidade humoral e celular em baco e intestino de camundongos isogenicos imunizados com taquizoitos irradiados por cobalto 60

    Energy Technology Data Exchange (ETDEWEB)

    Galisteo, Junior, Andres Jimenez

    2008-07-01

    We are developing a vaccine for toxoplasmosis, using ionizing radiation as a tool. Here we analyzed the production of systemic and intestinal immunity, with protection studies, in several strains of inbred mice, by oral or parenteral route, using 255 Gy irradiated tachyzoites of T. gondii RH strain, with challenge with cysts of ME- 49 strain. C57Bl/6j, BALB/c and C57Bl/6j IFN-{gamma}{sup -/-} mice were immunized with 10{sup 7} irradiated tachyzoites, be parenteral or oral route. Those preparations, both by parenteral or oral routes, induced the production of specific IgG, mainly of the lgG2b subclass, and IgA immunoglobulins in serum, , as determined by ELISA. IgM production was negligible. Parenteral immunized mice showed higher IgG avidity maturation, as compared to oral immunized mice. Fecal excretion of IgG, IgA and IgM was detected in stools of immunized animals, more intense in oral immunized mice. In cellular immunity studies, induced by antigen, with detection of cytokine production by quantitative real-time PCR, there are a great production of IFN-y by spleen cells, with lower levels in Peyer patches cells, where there are a greater IL-2 production. Challenge studies in immunized mice demonstrated protection to infection in all used schedules, greater in BALB/c mice. C57Bl/6j IFN-{gamma} -{sup /-} mice, when immunized, showed no signs of disease and produced similar or greater levels of antibodies than wild type mice. They also excreted S-lgA and S-IgM in stools, but with low numbers of brain cysts in parenteral immunized mice, despite similar mortality. Our data points to a fair possibility of use of those irradiated parasites as an oral vaccine, devised to use for veterinary or wild felines vaccination, reducing the production of oocysts by those hosts and interrupting the chain transmission of human toxoplasmosis. (author)

  11. Preliminary experimental study on splenic hemodynamics of radiofrequency ablation for the spleen.

    Science.gov (United States)

    Baba, Yasutaka; Hayashi, Sadao; Nagasato, Kohei; Higashi, Michiyo; Yoshiura, Takashi

    2017-08-01

    To test the splenic blood flow change after radiofrequency ablation (RFA) of the spleen in a porcine experimental model. Six pigs underwent RFA of the spleen via laparotomy. During the procedure of RFA, clamping of splenic artery (one) and both splenic artery/vein (one) was also performed. Measurement of blood flow of both splenic artery (SA) and splenic vein (SV) with flow-wire at pre- and post-RFA of the spleen was also performed. Ablated splenic lesions were created as estimating ∼50% area of the spleen in all pigs. Resected specimens reveal not only the coagulated necrosis but also the congestion of the spleen. On the SA hemodynamics, maximum peak velocity (MPV) changed from 37 ± 7 to 24 ± 8 cm/s (normal), 11 to 10 cm/s (clamp of the SA), and 12 to 7.5 cm/s (clamp of both SA/SV), respectively. On the SV hemodynamic, MPV changed from 15 ± 5 to 13 ± 4 cm/s (normal), 17 to 15 cm/s (clamp of the SA), and 17 to 26 cm/s (clamp of both SA/SV), respectively. RFA of the spleen could induce coagulation necrosis and reduce the splenic arterial blood flow.

  12. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua; Guo, Renfeng; Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun; Zhu, Maoxiang

    2015-01-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4 + CD25 + FoxP3 + regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis

  13. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua [Beijing Institute of Radiation Medicine, Beijing (China); Guo, Renfeng [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun [Beijing Institute of Radiation Medicine, Beijing (China); Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  14. Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells into peripheral blood circulation.

    Science.gov (United States)

    Li, Wei; Wang, Guanjun; Cui, Jiuwei; Xue, Lu; Cai, Lu

    2004-11-01

    The aim of this study was to investigate the stimulating effect of low-dose radiation (LDR) on bone marrow hematopoietic progenitor cell (HPC) proliferation and peripheral blood mobilization. Mice were exposed to 25- to 100-mGy x-rays. Bone marrow and peripheral blood HPCs (BFU-E, CFU-GM, and c-kit+ cells) were measured, and GM-CSF, G-CSF, and IL-3 protein and mRNA expression were detected using ELISA, slot blot hybridization, and Northern blot methods. To functionally evaluate LDR-stimulated and -mobilized HPCs, repopulation of peripheral blood cells in lethally irradiated recipients after transplantation of LDR-treated donor HPCs was examined by WBC counts, animal survival, and colony-forming units in the recipient spleens (CFUs-S). 75-mGy x-rays induced a maximal stimulation for bone marrow HPC proliferation (CFU-GM and BFU-E formation) 48 hours postirradiation, along with a significant increase in HPC mobilization into peripheral blood 48 to 72 hours postradiation, as shown by increases in CFU-GM formation and proportion of c-kit+ cells in the peripheral mononuclear cells. 75-mGy x-rays also maximally induced increases in G-CSF and GM-CSF mRNA expression in splenocytes and levels of serum GM-CSF. To define the critical role of these hematopoietic-stimulating factors in HPC peripheral mobilization, direct administration of G-CSF at a dose of 300 microg/kg/day or 150 microg/kg/day was applied and found to significantly stimulate GM-CFU formation and increase c-kit+ cells in the peripheral mononuclear cells. More importantly, 75-mGy x-rays plus 150 microg/kg/day G-CSF (LDR/150-G-CSF) produced a similar effect to that of 300 microg/kg/day G-CSF alone. Furthermore, the capability of LDR-mobilized donor HPCs to repopulate blood cells was confirmed in lethally irradiated recipient mice by counting peripheral WBC and CFUs-S. These results suggest that LDR induces hematopoietic hormesis, as demonstrated by HPC proliferation and peripheral mobilization, providing a

  15. UV-Induced Cell Death in Plants

    Science.gov (United States)

    Nawkar, Ganesh M.; Maibam, Punyakishore; Park, Jung Hoon; Sahi, Vaidurya Pratap; Lee, Sang Yeol; Kang, Chang Ho

    2013-01-01

    Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400–700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280–320 nm) and UV-A (320–390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD). PMID:23344059

  16. Cell shape changes induced by cationic anesthetics

    Science.gov (United States)

    1976-01-01

    The effects of local anesthetics on cultivated macrophages were studied in living preparations and recorded in still pictures and time-lapse cine-micrographs. Exposure to 12mM lidocaine or 1.5 mM tetracaine resulted in rounding in 10-15 min. Rounding was characterized by cell contraction, marked increase in retraction fibrils, withdrawal of cell processes, and, in late stages, pulsation-like activity and zeiosis. Cells showed appreciable membrane activity as they rounded. Respreading was complete within 15 min of perfusion in drug-free medium and entailed a marked increase in surface motility over control periods. As many as eight successive cycles of rounding and spreading were obtained with lidocaine without evidence of cell damage. The effects of anesthetics were similar to those observed with EDTA, but ethylene- glycol-bis(beta-aminoethylether)-N, N'-tetraacetic acid-Mg was ineffective. Rounding was also induced by benzocaine, an anesthetic nearly uncharged at pH 7.0. Quaternary (nondischargeable) compounds were of low activity, presumably because they are slow permeants. Lidocaine induced rounding at 10 degrees C and above but was less effective at 5 degrees C and ineffective at 0 degrees C. Rounding by the anesthetic was also obtained in media depleted or Na or enriched with 10 mM Ca or Mg. The latter finding, together with the failure of tetrodotoxin to induce rounding, suggests that the anesthetic effect is unrelated to inhibition of sodium conductance. It is possible that the drugs influence divalent ion fluxes or some component of the contractile cells' machinery, but a metabolic target of action cannot yet be excluded. PMID:814194

  17. Radiation-induced decrease of CD8+ dendritic cells contributes to Th1/Th2 shift.

    Science.gov (United States)

    Liu, Hu; Li, Bailong; Jia, Xiaojing; Ma, Yan; Gu, Yifeng; Zhang, Pei; Wei, Qun; Cai, Jianming; Cui, Jianguo; Gao, Fu; Yang, Yanyong

    2017-05-01

    Exposure to ionizing radiation (IR) often reduce the helper T (Th) 1 like function, resulting in a Th1/Th2 imbalance, which could affect the efficacy of cancer radiotherapy. As the most potent antigen presenting cells, dendritic cells (DC) can be divided into several subsets with specialized function. However, there is no literature covering the changes of DC subsets and their roles in immune regulation in response to IR. In the present study, we were aimed to investigate the changes of DC subsets after IR and its relationship with Th1/Th2 immunity. We found a significant decrease of BDCA3+DC in the blood of patients treated with radiotherapy. CD8+DC, a mouse equivalent of human BDCA3+DC, was also found decreased in mice spleen, peripheral blood and lymph node tissues after irradiation. As CD8+DC mainly induce Th1 immunity, we tested the changes of Th1/Th2 response and found that IR caused a repression of Th1 immunity, indicating a possible role of CD8+DC in radiation-induced Th1/Th2 imbalance. We also found that a CD8+DC-inducing cytokine, Fms-like tyrosine kinase 3 ligand (FLT3 ligand), restored CD8+DC and reversed Th1/Th2 shift. And then we found that bone marrow cells from irradiated mice differentiated into less CD8+DC, which was also protected by FLT3 ligand. In conclusion, our data showed that IR induced a decrease of CD8+DC and Th1/Th2 shift, which was reversed by Flt3 ligand treatment, suggesting a novel mechanism for radiation-induced immunosuppression. Copyright © 2017. Published by Elsevier B.V.

  18. Concanavalin A-induced activation of lymphocytic choriomeningitis virus memory lymphocytes into specifically cytotoxic T cells

    DEFF Research Database (Denmark)

    Marker, O; Thomsen, Allan Randrup; Andersen, G T

    1977-01-01

    When spleen cells, which have been primed to Lymphocytic Choriomeningitis (LCM) virus during a primary infection several months previously, are stimulated in vitro with Con A. highly specific secondary cytotoxic effector cells are generated. The degree of cytotoxicity revealed by such Con A...

  19. Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model

    International Nuclear Information System (INIS)

    Chang, Chi-Young; Lee, Jienny; Kim, Eun-Young; Park, Hae-Jung; Kwon, Choon-Hyuck; Joh, Jae-Won; Kim, Sung-Joo

    2007-01-01

    The novel cytokine, interleukin (IL)-18, is a strong interferon-γ inducer and costimulatory factor in Th1 cell activation. IL-18 triggers IFN-γ production and enhances cytolytic activity in both T and NK cells. However, the exact mechanism of antitumor action of IL-18 remains to be clarified. To determine the effects of IL-18 plasmid DNA on hepatic cancer in mice, CT26 murine colon adenocarcinoma cells were established in mouse liver. Plasmid vectors encoding IL-18 were transferred directly into the liver 7 days after tumor injection to restrict IL-18 expression within the tumor site. The IL-18 protein level was increased in the liver 4 days after plasmid injection, and a marked antitumoral effect was observed at day 7. Antitumor effects were evaluated by measuring tumor regression, immune cell population, and IFN-γ production. The IL-18 plasmid controlled the growth of hepatic tumors and proliferation of splenic immune cells. Moreover, treatment of CT26 tumors with the IL-18 plasmid significantly enhanced the population of the effector T and NK cells in the spleen and peripheral blood. In spleen, the population of CD4 + CD62 Low cells was augmented in response to IL-18 on day 7. These results are consistent with the increase in CD4 + T cells secreting IFN-γ, but not CD8 + T cells. The marked reduction of tumor growth in tumor-bearing mice was associated with the maintenance of IFN-γ production in spleen in response to IL-18. These antitumoral effects were maintained until 14 days after plasmid injection. Our results suggest that direct plasmid DNA transfer of IL-18 with no accompanying reagents to augment transfection efficiency may be useful in tumor immunotherapy

  20. An endogenous aryl hydrocarbon receptor (AhR) ligand, ITE induces regulatory T cells (Tregs) and ameliorates experimental colitis.

    Science.gov (United States)

    Abron, Jessicca D; Singh, Narendra P; Mishra, Manoj K; Price, Robert L; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Singh, Udai P

    2018-04-19

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if nontoxic ligand of AhR, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulphate (DSS)-induced colitis. Our studies demonstrated that in mice that received ITE treatment, in-vivo colitis pathogenesis, including a decrease in body weight, was significantly reversed along with the systemic and intestinal inflammatory cytokines. ITE increased the expression of Tregs in spleen, mesenteric lymph nodes (MLNs) and colon lamina propria lymphocytes (cLPL) of mice with colitis when compared to controls. This induction of Tregs was reversed by AhR antagonist treatment in-vitro. ITE treatment also increased dendritic cells (DCs; CD11c+) and decreased F4/80+ (macrophage) from the spleen, MLNs and cLPL in mice with colitis. ITE also reversed the systemic and intestinal frequency of CD4+T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6 and IL-1 as well as induced IL-10 levels. These findings suggest that ITE attenuates colitis through induction of Tregs and reduction in inflammatory CD4+ T cells and cytokines. Thus, our work demonstrates that the nontoxic endogenous AhR ligand ITE, may serve as a therapeutic modality to treat IBD.

  1. Hematopoietic differentiative properties of murine spleen implanted in the omenta of irradiated and nonirradiated hosts

    Energy Technology Data Exchange (ETDEWEB)

    Haley, J E; Tjio, J H; Smith, W W; Brecher, G [California Univ., San Francisco (USA); National Inst. of Arthritis, Metabolism, and Digestive Diseases, Bethesda, Md. (USA); National Cancer Inst., Bethesda, Md. (USA). Lab. of Viral Oncology)

    1975-01-01

    Whole body irradiation of the recipients of syngeneic splenic implants into the omentum greatly enhances hematopoiesis and permits survival of and repopulation by stem cells of donor origin. Donor hematopoietic stem cells do not survive in spleen implants of the nonirradiated host.Irradiated hosts were therefore used in the bulk of the experiments. Differentiation in the implants of splenic fragments is predominantly erythrocytic at 10 days and shifts to predominantly granulocytic differentiation at 21 days. Suspensions of spleen cells injected into the omentum are predominantly granulocytopoietic at 10 days. The differentiation in fragments of spleen depleted of stem cells by irradiation, seeded with bone marrow cells and implanted into the omentum results in mixed erythrocytic and granulocytic hematopoiesis, with granulocytic predominance. Lymphocytic cells appeared late in the implants of irradiated recipients even at a time of prolific lymphocytopoiesis in the hosts' own spleens. The cause of the delay in the implants is not clear. The data are consistent with the concept that differentiation of hematopoietic stem cells is influenced by the stromal cells of the parent organ. The erythrocytic inductive capacity of the stromal cells may belost by mechanical disruption or modified by irradiation or a prolonged period of implantation.

  2. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    Science.gov (United States)

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

  3. Imaging of the spleen: a proposed algorithm

    International Nuclear Information System (INIS)

    Shirkhoda, A.; McCartney, W.H.; Staab, E.V.; Mittelstaedt, C.A.

    1980-01-01

    The /sup 99m/Tc sulfur colloid scan is an effective initial method for evaluating splenic size, position, and focal or diffusely altered radionuclide uptake. Sonography is a useful next step in determining whether focal lesions are solid or cystic and the relation of the spleen to adjacent organs. In our opinion, computed tomography (CT) may be reserved for the few instances in which diagnostic questions remain unanswered after radionuclide scanning and sonography. Angiography is used primarily in splenic trauma. We evaluated 900 patients suspected of having liver-spleen abnormality. This experience, which led to a logically sequenced noninvasive imaging approach for evaluating suspected splenic pathology, is summarized and illustrated by several cases

  4. Imaging of the spleen: a proposed algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Shirkhoda, A.; McCartney, W.H.; Staab, E.V.; Mittelstaedt, C.A.

    1980-07-01

    The /sup 99m/Tc sulfur colloid scan is an effective initial method for evaluating splenic size, position, and focal or diffusely altered radionuclide uptake. Sonography is a useful next step in determining whether focal lesions are solid or cystic and the relation of the spleen to adjacent organs. In our opinion, computed tomography (CT) may be reserved for the few instances in which diagnostic questions remain unanswered after radionuclide scanning and sonography. Angiography is used primarily in splenic trauma. We evaluated 900 patients suspected of having liver-spleen abnormality. This experience, which led to a logically sequenced noninvasive imaging approach for evaluating suspected splenic pathology, is summarized and illustrated by several cases.

  5. ES-cell derived hematopoietic cells induce transplantation tolerance.

    Directory of Open Access Journals (Sweden)

    Sabrina Bonde

    Full Text Available BACKGROUND: Bone marrow cells induce stable mixed chimerism under appropriate conditioning of the host, mediating the induction of transplantation tolerance. However, their strong immunogenicity precludes routine use in clinical transplantation due to the need for harsh preconditioning and the requirement for toxic immunosuppression to prevent rejection and graft-versus-host disease. Alternatively, embryonic stem (ES cells have emerged as a potential source of less immunogenic hematopoietic progenitor cells (HPCs. Up till now, however, it has been difficult to generate stable hematopoietic cells from ES cells. METHODOLOGY/PRINCIPAL FINDINGS: Here, we derived CD45(+ HPCs from HOXB4-transduced ES cells and showed that they poorly express MHC antigens. This property allowed their long-term engraftment in sublethally irradiated recipients across MHC barriers without the need for immunosuppressive agents. Although donor cells declined in peripheral blood over 2 months, low level chimerism was maintained in the bone marrow of these mice over 100 days. More importantly, chimeric animals were protected from rejection of donor-type cardiac allografts. CONCLUSIONS: Our data show, for the first time, the efficacy of ES-derived CD45(+ HPCs to engraft in allogenic recipients without the use of immunosuppressive agents, there by protecting cardiac allografts from rejection.

  6. Oocyte-like cells induced from mouse spermatogonial stem cells.

    Science.gov (United States)

    Wang, Lu; Cao, Jinping; Ji, Ping; Zhang, Di; Ma, Lianghong; Dym, Martin; Yu, Zhuo; Feng, Lixin

    2012-08-06

    During normal development primordial germ cells (PGCs) derived from the epiblast are the precursors of spermatogonia and oogonia. In culture, PGCs can be induced to dedifferentiate to pluripotent embryonic germ (EG) cells in the presence of various growth factors. Several recent studies have now demonstrated that spermatogonial stem cells (SSCs) can also revert back to pluripotency as embryonic stem (ES)-like cells under certain culture conditions. However, the potential dedifferentiation of SSCs into PGCs or the potential generation of oocytes from SSCs has not been demonstrated before. We report that mouse male SSCs can be converted into oocyte-like cells in culture. These SSCs-derived oocytes (SSC-Oocs) were similar in size to normal mouse mature oocytes. They expressed oocyte-specific markers and gave rise to embryos through parthenogenesis. Interestingly, the Y- and X-linked testis-specific genes in these SSC-Oocs were significantly down-regulated or turned off, while oocyte-specific X-linked genes were activated. The gene expression profile appeared to switch to that of the oocyte across the X chromosome. Furthermore, these oocyte-like cells lost paternal imprinting but acquired maternal imprinting. Our data demonstrate that SSCs might maintain the potential to be reprogrammed into oocytes with corresponding epigenetic reversals. This study provides not only further evidence for the remarkable plasticity of SSCs but also a potential system for dissecting molecular and epigenetic regulations in germ cell fate determination and imprinting establishment during gametogenesis.

  7. Oocyte-like cells induced from mouse spermatogonial stem cells

    Directory of Open Access Journals (Sweden)

    Wang Lu

    2012-08-01

    Full Text Available Abstract Background During normal development primordial germ cells (PGCs derived from the epiblast are the precursors of spermatogonia and oogonia. In culture, PGCs can be induced to dedifferentiate to pluripotent embryonic germ (EG cells in the presence of various growth factors. Several recent studies have now demonstrated that spermatogonial stem cells (SSCs can also revert back to pluripotency as embryonic stem (ES-like cells under certain culture conditions. However, the potential dedifferentiation of SSCs into PGCs or the potential generation of oocytes from SSCs has not been demonstrated before. Results We report that mouse male SSCs can be converted into oocyte-like cells in culture. These SSCs-derived oocytes (SSC-Oocs were similar in size to normal mouse mature oocytes. They expressed oocyte-specific markers and gave rise to embryos through parthenogenesis. Interestingly, the Y- and X-linked testis-specific genes in these SSC-Oocs were significantly down-regulated or turned off, while oocyte-specific X-linked genes were activated. The gene expression profile appeared to switch to that of the oocyte across the X chromosome. Furthermore, these oocyte-like cells lost paternal imprinting but acquired maternal imprinting. Conclusions Our data demonstrate that SSCs might maintain the potential to be reprogrammed into oocytes with corresponding epigenetic reversals. This study provides not only further evidence for the remarkable plasticity of SSCs but also a potential system for dissecting molecular and epigenetic regulations in germ cell fate determination and imprinting establishment during gametogenesis.

  8. [Effects of herb cake-separated moxibustion on spleen in immunosuppressive rabbits:a morphology study].

    Science.gov (United States)

    Tian, Yuefeng; Wu, Aihua; Wang, Jun; Shan, Zengtian

    2016-10-12

    To observe the influence of different methods of moxibustion on spleen morphology in cyclophosphamide-induced immunosuppressive rabbits. A total of 50 rabbits were randomly assigned into a blank group, a model group, a herbal cake-separated moxibustion group, a moxibustion group and a sham cake-separated moxibustion group, 10 rabbits in each group. Except the blank group, the rabbits in each group were treated with intraperitoneal injection of cyclophosphamide (60 mg/kg), once a day, for 7 consecutive days to establish immunosuppressive model. After the model establishment, the rabbits in the herbal cake-separated moxibustion group were treated with herbal cake-separated moxibustion at "Shenque" (CV 8), "Guanyuan" (CV 4), "Zusanli" (ST 36), "Pishu" (BL 20) and "Shenshu" (BL 23); the moxa cone was placed on the herbal cake which was made of Liuwei Dihuang decoction, three cones for each acupoint. The rabbits in the moxibustion group were treated with moxa stick moxibustion which contained equal moxa of three moxa cones. The rabbits in the sham cake-separated moxibustion group were treated with cake which was made of flour. The acupoint selection in the above three groups was identical, and the intervention was given once every other day for totally 10 times. The rabbits in the blank group and model group were immobilized for identical time without any intervention. After treatment, the rabbits were sacrificed to collect the spleen. With routine HE staining, the morphology changes of spleen were observed under microscope. In addition, the white pulp, splenic corpuscle and the counts of lymphatic cells of lymphatic sheath around the arteries were observed. Compared with the blank group, the average size of white pulp and the radius of splenic corpuscle were reduced (both P 0.05). Compared with the model group, the averagesize of white pulp and the radius of splenic corpuscle were significantly increased in the herbal cake-separated moxibustion group and moxibustion

  9. Immunological response induced by cryoablation against murine H22 hepatoma cell line in vivo.

    Science.gov (United States)

    Yang, Xueling; Li, Xiaoli; Guo, Zhi; Si, Tongguo; Yu, Haipeng; Xing, Wenge

    2018-02-01

    To describe immunological consequences induced by cryoablation against H22 cells in vivo. Adult BALB/c mice underwent subcutaneous implantation of H22 cells. All of them were assigned into three groups randomly: group A (false surgery), group B (cryoablation) and group C (cryoablation plus Freund's adjuvant). Animals were sacrificed 1, 2 and 3 weeks after treatment. Serum IFN-γ and IL-4, Th1/Th2 in spleens and cytotoxicity were detected. Compared with that of group A, (1) INF-γ of group B was higher, but IL-4 was lower; cryoablation plus Freund's adjuvant enhanced these effects. (2) Th1/Th2 rose significantly in both group B and group C. (3) Strong cytolytic activity against H22 cells of group B and group C was found on day 7, 14 and 21. Our study showed a marked shift toward Th1 and IFN-γ expression after cryoablation, with an immuno-stimulatory effect against murine H22 hepatoma Cell. Copyright © 2017. Published by Elsevier Inc.

  10. Laparoscopic splenectomy for a simultaneous wandering spleen along with an ectopic accessory spleen. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Antonia Rizzuto

    Full Text Available Background: Wandering spleen and accessory spleen are uncommon entity occurring during embryonic development. Wandering spleen results in an excessive mobility and migration of the spleen from its normal position in the left hypochondrium while accessory spleen is characterized by ectopic splenic masses or tissue disjointed from the main body of spleen.Due to the nonspecific and multiple symptoms the clinical diagnosis of both conditions is uncertain even with imaging techniques, such as CT and MRI. The coexistence of both diseases (wandering spleen ad accessory spleen is uncommon. Case report: A 17–year old European female with a history of minor beta thalassemia and recurrent attacks of abdominal pain. Pre- operative management consisted of routine laboratory tests, ultrasound, CT scan. An ectopic spleen along with an accessory spleen were diagnosed. After a multidisciplinary board a laparoscopic splenectomy was performed. Post-operative recovery was uneventful, and the patient was discharged on the 6th post-operative day with the indication to continue the therapy with low molecular weight heparin (LMWH for 30 days Conclusions: This case represents a simultaneous condition of wandering splenomegaly along with an ectopic wandering spleen. The coexistence of these two rare conditions is peculiar such as the age of the patient, as literature reports such diseases to affect children or more commonly people in the range of 20–40 years of age. Laparoscopic treatment for this particular condition is also unusual. Keywords: Ectopic spleen, Wandering spleen, Laparoscopic splenectomy

  11. The time-course relationship between endogenous spleen colony formation and marrow cellularity after midlethal irradiation of mice

    International Nuclear Information System (INIS)

    Koch, I.; Wiktor-Jedrzejczak, W.; Wojskowa Akademia Medyczna, Warsaw

    1981-01-01

    The kinetics of appearance and disappearance of endogenous spleen colonies following 4 and 6 Gy of X-irradiation was compared with the kinetics of changes of cellular contents of femur cavities. Additionally, the effect of postirradiation bleeding and this way of the subsequent increase in the level of endogenous erythropoietin was studied. It was found that the kinetics of endogenous haemopoietic recovery in the marrow follows the same characteristic biphasic pattern as in the spleen although it is slightly delayed in time. First wave of regeneration corresponded in time with the formation of transient endogenous spleen colonies 4-7 days postirradiation, and the 2nd wave corresponded in time witn the formation of classical haemopoietic stem-cell derived endogenous spleen colonies 9-12 days following irradiation. Postirradiation bleeding markedly stimulated particularly the first wave of regeneration both in the marrow and in the spleen. (orig.) [de

  12. Value of transoperative scintigraphy in the detection of accessory spleens

    International Nuclear Information System (INIS)

    Sezeur, A.; Goujard, F.; Labriolle-Vaylet, C.L. de; Wioland, M.; Douay, L.; Desmarquet, J.

    1990-01-01

    A case of accessory spleen, 1 cm in diameter, responsible for recurrence of an idiopathic thrombocytopenic purpura after splenectomy is reported. This case is original in that the accessory spleen could only be detected by transoperative scintigraphy. Transoperative scintigraphy is a simple method to be used when one or several unrecognized accessory spleens are responsible for recurrence of a blood disease after excision of the principal spleen [fr

  13. H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

    International Nuclear Information System (INIS)

    Lannin, D.R.; Yu, S.; McKhann, C.F.

    1982-01-01

    It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F 1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F 1 hybrid bone marrow. The F 1 → C3H chimera but not the F 1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F 1 → C57BL/6 chimera but not the F 1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

  14. The spleen in the sickling disorders: an update

    International Nuclear Information System (INIS)

    Khatib, Rana; Sarnaik, Sharada A.; Rabah, Raja

    2009-01-01

    In early life, patients with sickle cell disease (SCD) can have acute, life-threatening emergencies related to splenic hypofunction (overwhelming bacterial sepsis), as well as anemic crises from acute splenic sequestration because of sudden pooling of blood in the spleen. The landmark penicillin prophylaxis study in 1985 showed a remarkable decrease in mortality from sepsis in young children with SCD who were treated with oral penicillin prophylaxis compared to placebo. Since that study, newborns are screened for SCD and placed on oral penicillin prophylaxis in nearly all of the United States, as well as in other countries where the disease is highly prevalent. The previously described permanent, complete and nearly universal ''autosplenectomy'' emerging by late childhood or early adulthood is now challenged by recent findings of reversibility of splenic dysfunction by the antisickling drug hydroxyurea or by successful allogeneic stem cell transplantation, even in older patients. Imaging techniques for hypofunction of the spleen are the most commonly used modalities to guide the clinician in decisions regarding medical or surgical management. (orig.)

  15. The spleen in the sickling disorders: an update

    Energy Technology Data Exchange (ETDEWEB)

    Khatib, Rana; Sarnaik, Sharada A. [Wayne State University School of Medicine, Children' s Hospital of Michigan, Carmen and Ann Adams Department of Pediatrics, Detroit, MI (United States); Rabah, Raja [Wayne State University School of Medicine, Department of Pathology, Detroit, MI (United States)

    2009-01-15

    In early life, patients with sickle cell disease (SCD) can have acute, life-threatening emergencies related to splenic hypofunction (overwhelming bacterial sepsis), as well as anemic crises from acute splenic sequestration because of sudden pooling of blood in the spleen. The landmark penicillin prophylaxis study in 1985 showed a remarkable decrease in mortality from sepsis in young children with SCD who were treated with oral penicillin prophylaxis compared to placebo. Since that study, newborns are screened for SCD and placed on oral penicillin prophylaxis in nearly all of the United States, as well as in other countries where the disease is highly prevalent. The previously described permanent, complete and nearly universal ''autosplenectomy'' emerging by late childhood or early adulthood is now challenged by recent findings of reversibility of splenic dysfunction by the antisickling drug hydroxyurea or by successful allogeneic stem cell transplantation, even in older patients. Imaging techniques for hypofunction of the spleen are the most commonly used modalities to guide the clinician in decisions regarding medical or surgical management. (orig.)

  16. Spleen lymphocyte function modulated by a cocoa-enriched diet.

    Science.gov (United States)

    Ramiro-Puig, E; Pérez-Cano, F J; Ramírez-Santana, C; Castellote, C; Izquierdo-Pulido, M; Permanyer, J; Franch, A; Castell, M

    2007-09-01

    Previous studies have shown the down-regulating in vitro effect of cocoa flavonoids on lymphocyte and macrophage activation. In the present paper, we report the capacity of a long-term rich cocoa diet to modulate macrophage cytokine secretion and lymphocyte function in young rats. Weaned rats received natural cocoa (4% or 10% food intake), containing 32 mg flavonoids/g, for 3 weeks. Spleen immune function was then evaluated through the analysis of lymphocyte composition, their proliferative response and their ability to secrete cytokines and Ig. In addition, the status of activated peritoneal macrophages was established through tumour necrosis factor (TNF)-alpha secretion. The richest cocoa diet (10%) caused a reduction of TNF-alpha secretion by peritoneal macrophages showing anti-inflammatory activity. Similarly, although a 10% cocoa diet increased lymphocyte proliferation rate, it down-regulated T helper 2 (Th2)-related cytokines and decreased Ig secretion. These changes were accompanied by an increase in spleen B cell proportion and a decrease in Th cell percentage. In summary, these results demonstrate the functional activity of a cocoa-high dosage in down-regulating the immune response that might be beneficial in hypersensitivity and autoimmunity.

  17. A wandering spleen presenting as a hypogastric mass: Case report ...

    African Journals Online (AJOL)

    ... the spleen. A 26-year-old woman was admitted to our hospital with vomiting and abdominal pain. Abdominal examination revealed a large ovoid hypogastric mass. A CT scan showed a wandering spleen in the hypogastric region. Exploratory laparotomy revealed an ischemic spleen. A total splenectomy was performed.

  18. A minimally invasive approach to spleen histopathology in dogs: A new method for follow-up studies of spleen changes in the course of Leishmania infantum infection.

    Science.gov (United States)

    Santos, Silvana Ornelas; Fontes, Jonathan L M; Laranjeira, Daniela F; Vassallo, José; Barrouin-Melo, Stella Maria; Dos-Santos, Washington L C

    2016-10-01

    Severe forms of zoonotic visceral leishmaniosis (ZVL) are associated with disruption of the spleen structure. However, the study of spleen histology requires splenectomy or necropsy. In this work, we present a minimally invasive cell-block technique for studying spleen tissue histology in dogs with ZVL. We examined 13 dogs with and seven dogs without Leishmania infantum infection. The dogs with Leishmania infection had a lower frequency of lymphoid follicles (2/13, Fisher's test, Pdogs (5/7 exhibiting lymphoid follicles and a plasma cell score of 1). The dogs with Leishmania infection also presented with granulomas (8/13) and infected macrophages (5/13). These differences in the histological presentations of spleen tissue from infected and uninfected dogs corresponded to changes observed in conventional histology. Hence, the cell-block technique described here may be used in the follow-up care and study of dogs with ZVL and other diseases in both clinical practice and research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Stimulatory and cytotoxic effects of beryllium on proliferation of mouse spleen lymphocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Price, R.J.; Skilleter, D.N.

    1985-01-01

    Low concentrations (1-5 ..mu..M) of beryllium (Be) salts were weakly mitogenic to mouse spleen cells in vitro as measured by an hydroxyurea-sensitive 2-3fold increase in pulse labelled (/sup 3/H)-thymidine incorporation into lymphocyte DNA. It is proposed the activation may be induced by a direct interaction of Be/sup 2 +/ with the lymphocyte membranes. Higher concentrations of Be/sup 2 +/ (5-20 ..mu..M) produced a gradual loss of the stimulatory response, possibly as the result of either a limited cytotoxic effect or by the established property of intracellularly-accumulated Be/sup 2 +/ to inhibit cell division. In contrast, Concanavalin A-stimulated lymphocyte mitogenesis was markedly decreased by a 20-h-preincubation of splenocytes with micromolar concentrations of Be/sup 2 +/, whereas similar pretreatment with lower concentrations (0.1 ..mu..M) actually enchanced the subsequent proliferative response. In both cases, supplementary addition of 0.1-1% peritoneal macrophages increased the level of Concanavalin A stimulation. It is concluded, therefore, that inhibition of the proliferative response to accessory cell-dependent mitogens may result from a dose-dependent destruction by Be/sup 2 +/ of the macrophage/adherent cell population.

  20. Effect of serum from rats with destructed nuclei of the posterior hypothalamus on the formation of hemopoietic colonies in the spleen of lethally irradiated mice after bone marrow cell transplantation

    International Nuclear Information System (INIS)

    Fedorov, N.A.; Likhovetskaya, Z.M.; Kurbanova, G.N.; Prigozhina, T.A.; L'vovich, A.I.

    1982-01-01

    Colony formation capability of serum from animals with destructed nuclei of the posterior hypothalamus was studied in lethally irradiated mice. Male-rats of Wistar line and hybrid mice (CBA x C57 BL) were used in the experiments. The serum from rats with destructed nuclei of the posterior hypothalamus was injected simultaneously with bone marrow transplantation into lethally irradiated mice. The number of macrocolonies in the spleen was counted on the 9th day. It was ascertained that the serum from rats with destructed nuclei of the posterior hypothalamus caused an increase of the number of macroscopically visible colonies in the spleen of lethally irradiated mice. The determination of hemopoetic types of colonies showed that the effect of the serum from those animals caused an increase of the number of granulocytic-type colonies. The initiation of colony stimulating and leukopoetic activity in the blood of animals after the destruction of mammillary body nuclei and posterior hypothalamic nucleus attested, according to the authors point of view, that humoral mediators (humoral mediator) could participated in the mechanism of hypothalamus effect on leulopoiesis

  1. Induced Pluripotent Stem Cells Meet Genome Editing.

    Science.gov (United States)

    Hockemeyer, Dirk; Jaenisch, Rudolf

    2016-05-05

    It is extremely rare for a single experiment to be so impactful and timely that it shapes and forecasts the experiments of the next decade. Here, we review how two such experiments-the generation of human induced pluripotent stem cells (iPSCs) and the development of CRISPR/Cas9 technology-have fundamentally reshaped our approach to biomedical research, stem cell biology, and human genetics. We will also highlight the previous knowledge that iPSC and CRISPR/Cas9 technologies were built on as this groundwork demonstrated the need for solutions and the benefits that these technologies provided and set the stage for their success. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Sorafenib-induced defective autophagy promotes cell death by necroptosis

    OpenAIRE

    Kharaziha, Pedram; Chioureas, Dimitris; Baltatzis, George; Fonseca, Pedro; Rodriguez, Patricia; Gogvadze, Vladimir; Lennartsson, Lena; Bj?rklund, Ann-Charlotte; Zhivotovsky, Boris; Grand?r, Dan; Egevad, Lars; Nilsson, Sten; Panaretakis, Theocharis

    2015-01-01

    Autophagy is one of the main cytoprotective mechanisms that cancer cells deploy to withstand the cytotoxic stress and survive the lethal damage induced by anti-cancer drugs. However, under specific conditions, autophagy may, directly or indirectly, induce cell death. In our study, treatment of the Atg5-deficient DU145 prostate cancer cells, with the multi-tyrosine kinase inhibitor, sorafenib, induces mitochondrial damage, autophagy and cell death. Molecular inhibition of autophagy by silencin...

  3. MHC Expression on Spleen Lymphocyte Subsets in Genetically Resistant and Susceptible Chickens Infected with Marek's Disease Virus

    DEFF Research Database (Denmark)

    Dalgaard, Tina; Bøving, Mette K.; Handberg, Kurt

    2009-01-01

    cytometry for MHC surface expression. In the spleen, constitutive MHC class I surface expression was found to be highest in homozygous B19, lowest in homozygous B21, and intermediate in heterozygous B19/B21 animals. This was observed on CD4(+), CD8(+), and Bu-1(+) splenic lymphocytes. Chickens of all three...... genotypes were subjected to infection with MD virus (GA strain) and spleen samples from infected as well as MHC-matched negative controls were analyzed at 1, 4, and 8 wk post-infection (p.i.). It was observed that MDV induced an increase in MHC class I expression late in the infection. Thus, MHC class I...... was increased on the surface of CD4(+) cells from infected chickens of all genotypes at 4 and 8 wk p.i. compared with negative controls. Also, MHC class I expression was increased on CD8(+) cells from infected chickens of all genotypes at 4 and 8 wk p.i., except for the homozygous B19 animals, that showed...

  4. In vivo evidence for CD4+ and CD8+ suppressor T cells in vaccination-induced suppression of murine experimental autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Flynn, J.C.; Kong, Y.C.

    1991-01-01

    In several experimental autoimmune diseases, including experimental autoimmune thyroiditis (EAT), vaccination with attenuated autoantigen-specific T cells has provided protection against subsequent induction of disease. However, the mechanism(s) of vaccination-induced suppression remains to be clarified. Since the authors have previously shown that suppression generated by pretreatment with mouse thyroglobulin (MTg) or thyroid-stimulating hormone in EAT is mediated by CD4+, not CD8+, suppressor T cells, they examined the role of T cell subsets in vaccination-induced suppression of EAT. Mice were vaccinated with irradiated, MTg-primed, and MTg-activated spleen cells and then challenged. Pretreatment with these cells suppressed EAT induced by immunization with MTg and adjuvant, but not by adoptive transfer of thyroiditogenic cells, suggesting a mechanism of afferent suppression. The activation of suppressor mechanisms did not require CD8+ cells, since mice depleted of CD8+ cells before vaccination showed reduced EAT comparable to control vaccinated mice. Furthermore, depletion of either the CD4+ or the CD8+ subset after vaccination did not significantly abrogate suppression. However, suppression was eliminated by the depletion of both CD4+ and CD8+ cells in vaccinated mice. These results provide evidence for the cooperative effects of CD4+ and CD8+ T cells in vaccination-induced suppression of EAT

  5. Ames hypopituitary dwarf mice demonstrate imbalanced myelopoiesis between bone marrow and spleen.

    Science.gov (United States)

    Capitano, Maegan L; Chitteti, Brahmananda R; Cooper, Scott; Srour, Edward F; Bartke, Andrzej; Broxmeyer, Hal E

    2015-06-01

    Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid-stimulating hormone, and prolactin. The phenotype of these mice demonstrates irregularities in the immune system with skewing of the normal cytokine milieu towards a more anti-inflammatory environment. However, the hematopoietic stem and progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice has not been well characterized. We found that there was a significant decrease in overall cell count when comparing the BM and spleen of 4-5 month old dwarf mice to their littermate controls. Upon adjusting counts to differences in body weight between the dwarf and control mice, the number of granulocyte-macrophage progenitors, confirmed by immunophenotyping and colony-formation assay was increased in the BM. In contrast, the numbers of all myeloid progenitor populations in the spleen were greatly reduced, as confirmed by colony-formation assays. This suggests that there is a shift of myelopoiesis from the spleen to the BM of Ames dwarf mice; however, this shift does not appear to involve erythropoiesis. The reasons for this unusual shift in spleen to marrow hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the decreased hormone levels in these mice. Copyright © 2015. Published by Elsevier Inc.

  6. Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development

    Science.gov (United States)

    Lenti, Elisa; Farinello, Diego; Penkov, Dmitry; Castagnaro, Laura; Lavorgna, Giovanni; Wuputra, Kenly; Tjaden, Naomi E. Butler; Bernassola, Francesca; Caridi, Nicoletta; Wagner, Michael; Kozinc, Katja; Niederreither, Karen; Blasi, Francesco; Pasini, Diego; Trainor, Paul A.

    2016-01-01

    The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome P450 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia. PMID:27214556

  7. Cell kinetic studies on radiation induced leukemogenesis

    International Nuclear Information System (INIS)

    Nakao, Isamu; Suzuki, Gen; Imai, Yasufumi; Kawase, Yoshiko; Nose, Masako; Hirashima, Kunitake; Bessho, Masami

    1989-01-01

    The purpose of this study was threefold: (1) to determine the clonal origin of radiation-induced thymic lymphoma in mice with cellular mosaicism for phosphoglycerate kinase; (2) to determine the incidence and latent period of myeloid leukemia and thymic lymphoma induced by whole-body exposure to median doses (3.0 Gy or less) in RFM/MsNrs-2 mice; and (3) to examine the influence of human recombinant interleukin-2 (hrIL-2). Thymic lymphoma was of a single cell origin. The incidence of radiation-induced myeloid leukemia and thymic lymphoma in RFM mice increased in a dose dependent fashion. Mean latent periods of both myeloid leukemia and thymic lymphoma after irradiation became shorter in proportion to radiation doses. When hrIL-2 was injected to RFM mice receiving 3.0 Gy, mean survivals were shorter in thymoma-bearing mice than the control mice. This suggested that hrIL-2 shortens the promotion step of thymoma. Administration of hrIL-2 failed to alter the incidence of myeloid leukemia or the mean survival of mice having myeloid leukemia, indicating that the protocol of hrIL-2 administration was not so sufficient as to alter the myeloid leukemogenesis. (Namekawa, K)

  8. Metastatic melanoma cells escape from immunosurveillance through the novel mechanism of releasing nitric oxide to induce dysfunction of immunocytes.

    Science.gov (United States)

    Zhang, X M; Xu, Q

    2001-12-01

    Nitric oxide (NO) is known to facilitate tumour metastasis through the promotion of angiogenesis, vascular dilation, platelet aggregation, etc. In the present study we explored its novel role in producing dysfunction of the host immune system in the metastasis of murine metastatic melanoma B16-BL6 cells. A significant reduction in the mixed lymphocyte reaction (MLR) was observed in the spleen cells from B16-BL6-bearing mice, but not in those from mice bearing the parent cell B16. When B16-BL6 cells were added in vitro to the MLR, a significant decrease was also found, even when they were co-cultured with the lymphocytes in two compartments of a Transwell chamber separated by an 8.0 microm filter. The supernatant from cultured B16-BL6 but not B16 cells, which had a greatly increased NO activity, significantly inhibited concanavalin A- and lipopolysaccharide-induced lymphocyte proliferation. A remarkably higher expression of inducible NO synthase (iNOS) was detected in B16-BL6 cells than in B16 cells. Nomega-Nitro-l-arginine (l-NNA), a NO synthase inhibitor and superoxide dismutase, significantly antagonized the above inhibition by B16-BL6 cells, while l-arginine, a NO precursor, and S-nitroso-N-acetyl-d,l-penicillamine, a NO donor, strengthened the inhibition. Furthermore, l-NNA significantly inhibited lung metastasis of B16-BL6 cells, while l-arginine tended to enhance the metastasis. The cytotoxicity of B16-BL6-specific T-cells was significantly decreased by pre-culture with B16-BL6 cells in a Transwell chamber or the culture supernatants of B16-BL6 cells, whereas l-iminoethyl-lysine, a selective inhibitor of iNOS, showed a significant recovery from the disease. These results suggest that NO released by metastatic tumour cells may impair the immune system, which facilitates the escape from immunosurveillance and metastasis of tumour cells.

  9. Pathologic rupture of the spleen in a patient with acute myelogenous leukemia and leukostasis

    Directory of Open Access Journals (Sweden)

    Gil Cunha De Santis

    2014-07-01

    Full Text Available Rupture of the spleen can be classified as spontaneous, traumatic, or pathologic. Pathologic rupture has been reported in infectious diseases such as infectious mononucleosis, and hematologic malignancies such as acute and chronic leukemias. Splenomegaly is considered the most relevant factor that predisposes to splenic rupture. A 66-year-old man with acute myeloid leukemia evolved from an unclassified myeloproliferative neoplasm, complaining of fatigue and mild upper left abdominal pain. He was pale and presented fever and tachypnea. Laboratory analyses showed hemoglobin 8.3 g/dL, white blood cell count 278 × 109/L, platelet count 367 × 109/L, activated partial thromboplastin time (aPTT ratio 2.10, and international normalized ratio (INR 1.60. A blood smear showed 62% of myeloblasts. The immunophenotype of the blasts was positive for CD117, HLA-DR, CD13, CD56, CD64, CD11c and CD14. Lactate dehydrogenase was 2384 U/L and creatinine 2.4 mg/dL (normal range: 0.7-1.6 mg/dL. Two sessions of leukapheresis were performed. At the end of the second session, the patient presented hemodynamic instability that culminated in circulatory shock and death. The post-mortem examination revealed infiltration of the vessels of the lungs, heart, and liver, and massive infiltration of the spleen by leukemic blasts. Blood volume in the peritoneal cavity was 500 mL. Acute leukemia is a rare cause of splenic rupture. Male gender, old age and splenomegaly are factors associated with this condition. As the patient had leukostasis, we hypothesize that this, associated with other factors such as lung and heart leukemic infiltration, had a role in inducing splenic rupture. Finally, we do not believe that leukapheresis in itself contributed to splenic rupture, as it is essentially atraumatic.

  10. Mechanisms of Betulinic acid‐induced cell death

    NARCIS (Netherlands)

    Potze, L.

    2015-01-01

    The scope of this thesis was to investigate the mechanisms by which BetA induces cell death in cancer cells in more detail. At the start of the studies described in this thesis several questions urgently needed an answer. Although BetA induces cell death via apoptosis, when blocking this form of

  11. Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.

    Science.gov (United States)

    Gururajan, Murali; Dasu, Trivikram; Shahidain, Seif; Jennings, C Darrell; Robertson, Darrell A; Rangnekar, Vivek M; Bondada, Subbarao

    2007-01-01

    Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

  12. IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing B lymphocytes and myeloid-derived suppressor cells.

    Science.gov (United States)

    Kulkarni, Upasana; Herrmenau, Christoph; Win, Stephanie J; Bauer, Michael; Kamradt, Thomas

    2018-01-01

    Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment. We analysed the frequencies and numbers of regulatory T cells (Tregs), double negative T cells, IL-10 producing B cells and myeloid-derived suppressor cells (MDSCs) for 3.5 months after sepsis induction. Sepsis induced an increase in IL-10+ B cells, which was enhanced and prolonged by IL-7 treatment. An increased frequency of MDSCs in the spleen was still detectable 3.5 months after sepsis induction and this was more pronounced in IL-7-treated mice. MDSCs from septic mice were more potent at suppressing T cell proliferation than MDSCs from control mice. Our data reveal that sepsis induces a long lasting increase in IL-10+ B cells and MDSCs. Late-onset IL-7 treatment augments this increase, which should be relevant for clinical interventions.

  13. Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS.

    Science.gov (United States)

    Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

    2003-05-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.

  14. Infection with Salmonella enterica Serovar Typhimurium Leads to Increased Proportions of F4/80+ Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen.

    Directory of Open Access Journals (Sweden)

    Kristin L Rosche

    Full Text Available Infection of mice with Salmonella enterica serovar Typhimurium (Salmonella causes systemic inflammatory disease and enlargement of the spleen (splenomegaly. Splenomegaly has been attributed to a general increase in the numbers of phagocytes, lymphocytes, as well as to the expansion of immature CD71+Ter119+ reticulocytes. The spleen is important for recycling senescent red blood cells (RBCs and for the capture and eradication of blood-borne pathogens. Conservation of splenic tissue architecture, comprised of the white pulp (WP, marginal zone (MZ, and red pulp (RP is essential for initiation of adaptive immune responses to captured pathogens. Using flow cytometry and four color immunofluorescence microscopy (IFM, we show that Salmonella-induced splenomegaly is characterized by drastic alterations of the splenic tissue architecture and cell population proportions, as well as in situ cell distributions. A major cause of splenomegaly appears to be the significant increase in immature RBC precursors and F4/80+ macrophages that are important for recycling of heme-associated iron. In contrast, the proportions of B220+, CD4+ and CD8+ lymphocytes, as well as MZ MOMA+ macrophages decrease significantly as infection progresses. Spleen tissue sections show visible tears and significantly altered tissue architecture with F4/80+ macrophages and RBCs expanding beyond the RP and taking over most of the spleen tissue. Additionally, F4/80+ macrophages actively phagocytose not only RBCs, but also lymphocytes, indicating that they may contribute to declining lymphocyte proportions during Salmonella infection. Understanding how these alterations of spleen microarchitecture impact the generation of adaptive immune responses to Salmonella has implications for understanding Salmonella pathogenesis and for the design of more effective Salmonella-based vaccines.

  15. Infection with Salmonella enterica Serovar Typhimurium Leads to Increased Proportions of F4/80+ Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen.

    Science.gov (United States)

    Rosche, Kristin L; Aljasham, Alanoud T; Kipfer, James N; Piatkowski, Bryan T; Konjufca, Vjollca

    2015-01-01

    Infection of mice with Salmonella enterica serovar Typhimurium (Salmonella) causes systemic inflammatory disease and enlargement of the spleen (splenomegaly). Splenomegaly has been attributed to a general increase in the numbers of phagocytes, lymphocytes, as well as to the expansion of immature CD71+Ter119+ reticulocytes. The spleen is important for recycling senescent red blood cells (RBCs) and for the capture and eradication of blood-borne pathogens. Conservation of splenic tissue architecture, comprised of the white pulp (WP), marginal zone (MZ), and red pulp (RP) is essential for initiation of adaptive immune responses to captured pathogens. Using flow cytometry and four color immunofluorescence microscopy (IFM), we show that Salmonella-induced splenomegaly is characterized by drastic alterations of the splenic tissue architecture and cell population proportions, as well as in situ cell distributions. A major cause of splenomegaly appears to be the significant increase in immature RBC precursors and F4/80+ macrophages that are important for recycling of heme-associated iron. In contrast, the proportions of B220+, CD4+ and CD8+ lymphocytes, as well as MZ MOMA+ macrophages decrease significantly as infection progresses. Spleen tissue sections show visible tears and significantly altered tissue architecture with F4/80+ macrophages and RBCs expanding beyond the RP and taking over most of the spleen tissue. Additionally, F4/80+ macrophages actively phagocytose not only RBCs, but also lymphocytes, indicating that they may contribute to declining lymphocyte proportions during Salmonella infection. Understanding how these alterations of spleen microarchitecture impact the generation of adaptive immune responses to Salmonella has implications for understanding Salmonella pathogenesis and for the design of more effective Salmonella-based vaccines.

  16. α-Mangostin Induces Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma Cell

    Directory of Open Access Journals (Sweden)

    Hyun-Ho Kwak

    2016-01-01

    Full Text Available Mangosteen has long been used as a traditional medicine and is known to have antibacterial, antioxidant, and anticancer effects. Although the effects of α-mangostin, a natural compound extracted from the pericarp of mangosteen, have been investigated in many studies, there is limited data on the effects of the compound in human oral squamous cell carcinoma (OSCC. In this study, α-mangostin was assessed as a potential anticancer agent against human OSCC cells. α-Mangostin inhibited cell proliferation and induced cell death in OSCC cells in a dose- and time-dependent manner with little to no effect on normal human PDLF cells. α-Mangostin treatment clearly showed apoptotic evidences such as nuclear fragmentation and accumulation of annexin V and PI-positive cells on OSCC cells. α-Mangostin treatment also caused the collapse of mitochondrial membrane potential and the translocation of cytochrome c from the mitochondria into the cytosol. The expressions of the mitochondria-related proteins were activated by α-mangostin. Treatment with α-mangostin also induced G1 phase arrest and downregulated cell cycle-related proteins (CDK/cyclin. Hence, α-mangostin specifically induces cell death and inhibits proliferation in OSCC cells via the intrinsic apoptosis pathway and cell cycle arrest at the G1 phase, suggesting that α-mangostin may be an effective agent for the treatment of OSCC.

  17. Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function

    Directory of Open Access Journals (Sweden)

    Phillips R

    2006-04-01

    Full Text Available Abstract Background Dendritic cells (DCs are central to the initiation and regulation of the adaptive immune response during infection. Modulation of DC function may therefore allow evasion of the immune system by pathogens. Significant depression of the host's systemic immune response to both concurrent infections and heterologous vaccines has been observed during malaria infection, but the mechanisms underlying this immune hyporesponsiveness are controversial. Results Here, we demonstrate that the blood stages of malaria infection induce a failure of DC function in vitro and in vivo, causing suboptimal activation of T cells involved in heterologous immune responses. This effect on T-cell activation can be transferred to uninfected recipients by DCs isolated from infected mice. Significantly, T cells activated by these DCs subsequently lack effector function, as demonstrated by a failure to migrate to lymphoid-organ follicles, resulting in an absence of B-cell responses to heterologous antigens. Fractionation studies show that hemozoin, rather than infected erythrocyte (red blood cell membranes, reproduces the effect of intact infected red blood cells on DCs. Furthermore, hemozoin-containing DCs could be identified in T-cell areas of the spleen in vivo. Conclusion Plasmodium infection inhibits the induction of adaptive immunity to heterologous antigens by modulating DC function, providing a potential explanation for epidemiological studies linking endemic malaria with secondary infections and reduced vaccine efficacy.

  18. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

    Science.gov (United States)

    Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

    2015-01-01

    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

  19. RNA-seq comparative analysis of Peking ducks spleen gene expression 24 h post-infected with duck plague virulent or attenuated virus.

    Science.gov (United States)

    Liu, Tian; Cheng, Anchun; Wang, Mingshu; Jia, Renyong; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Zhu, Dekang; Chen, Shun; Liu, Mafeng; Zhao, XinXin; Chen, Xiaoyue

    2017-09-13

    Duck plague virus (DPV), a member of alphaherpesvirus sub-family, can cause significant economic losses on duck farms in China. DPV Chinese virulent strain (CHv) is highly pathogenic and could induce massive ducks death. Attenuated DPV vaccines (CHa) have been put into service against duck plague with billions of doses in China each year. Researches on DPV have been development for many years, however, a comprehensive understanding of molecular mechanisms underlying pathogenicity of CHv strain and protection of CHa strain to ducks is still blank. In present study, we performed RNA-seq technology to analyze transcriptome profiling of duck spleens for the first time to identify differentially expressed genes (DEGs) associated with the infection of CHv and CHa at 24 h. Comparison of gene expression with mock ducks revealed 748 DEGs and 484 DEGs after CHv and CHa infection, respectively. Gene pathway analysis of DEGs highlighted valuable biological processes involved in host immune response, cell apoptosis and viral invasion. Genes expressed in those pathways were different in CHv infected duck spleens and CHa vaccinated duck spleens. The results may provide valuable information for us to explore the reasons of pathogenicity caused by CHv strain and protection activated by CHa strain.

  20. Induced adult stem (iAS) cells and induced transit amplifying progenitor (iTAP) cells-a possible alternative to induced pluripotent stem (iPS) cells?

    Science.gov (United States)

    Heng, Boon Chin; Richards, Mark; Ge, Zigang; Shu, Yimin

    2010-02-01

    The successful derivation of iPSC lines effectively demonstrates that it is possible to reset the 'developmental clock' of somatic cells all the way back to the initial embryonic state. Hence, it is plausible that this clock may instead be turned back half-way to a less immature developmental stage that is more directly applicable to clinical therapeutic applications or for in vitro pharmacology/toxicology screening assays. Such a suitable developmental state is postulated to be either the putative transit amplifying progenitor stage or adult stem cell stage. It is hypothetically possible to reprogram mature and terminally differentiated somatic cells back to the adult stem cell or transit amplifying progenitor stage, in a manner similar to the derivation of iPSC. It is proposed that the terminology 'Induced Adult Stem Cells' (iASC) or 'Induced Transit Amplifying Progenitor Cells' (iTAPC) be used to described such reprogrammed somatic cells. Of particular interest, is the possibility of resetting the developmental clock of mature differentiated somatic cells of the mesenchymal lineage, explanted from adipose tissue, bone marrow and cartilage. The putative adult stem cell sub-population from which these cells are derived, commonly referred to as 'mesenchymal stem cells', are highly versatile and hold much therapeutic promise in regenerative medicine, as attested to by numerous human clinical trials and animal studies. Perhaps it may be appropriate to term such reprogrammed cells as 'Induced Mesenchymal Stem Cells' (iMSC) or as 'Induced Mesenchumal Progenitor Cells' (iMPC). Given that cells from the same organ/tissue will share some commonalities in gene expression, we hypothesize that the generation of iASC or iTAPC would be more efficient as compared to iPSC generation, since a common epigenetic program must exist between the reprogrammed cells, adult stem cell or progenitor cell types and terminally differentiated cell types from the same organ/tissue.

  1. D2O-induced cell excitation

    International Nuclear Information System (INIS)

    Andjus, P.R.; Vucelic, D.

    1990-01-01

    The effects of deuterium oxide (D 2 O) on giant internodal cells of the fresh water alga Chara gymnophylla, were investigated. D 2 O causes membrane excitation followed by potassium leakage. The primary effect consists of an almost instantaneous membrane depolarization resembling an action potential with incomplete repolarization. A hypothesis was proposed which deals with an osmotic stress effect of D 2 O on membrane ion channels followed by the suppression of the electrogenic pump activity. The initial changes (potential spike and rapid K+ efflux) may represent the previously undetected link between the D 2 O-induced temporary arrest of protoplasmic streaming and the early events triggered at the plasma membrane level as the primary site of D 2 O action

  2. Human retinal pigment epithelial cell-induced apoptosis in activated T cells

    DEFF Research Database (Denmark)

    Jørgensen, A; Wiencke, A K; la Cour, M

    1998-01-01

    human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction...... of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells...... induced apoptosis in several activated T-cell populations and T-cell lines, including T-cell antigen receptor (TCR)-CD3-negative T-cell lines. In contrast, RPE cells induced little or no apoptosis in resting peripheral T cells. Major histocompatibility complex (MHC) class II monoclonal antibodies, which...

  3. Electronmicroscopic study of gamma irradiated mouse spleen during primary immune response

    International Nuclear Information System (INIS)

    Burneva, V.G.; Gitsov, L.G.; Boyadzhieva-Mikhajlova, A.; Kyncheva, L.S.; Viklichka, St.

    1978-01-01

    An electronmicroscopic study of the mouse spleen immunocompetent cells during the productive phase of the primary immune response after sublethal gamma ray irradiation is carried out. For this purpose the animals were immunized with sheep red blood cells 24 hours after irradiation and sacrified on the 5th day after immunization. The number of small lymphocytes is reduced in all zones of the spleen. Only in the periarteriolar area the lymphoid sheaths are well outlines and the ultrastructure of the cells preserved. Three types of reticulohistocytic elements, according to their radiosensitivity are observed. The most radioresistant cells are the fixed ''dark'' reticular cells which do not complete phagocytosis. The ultrastructure of their nucleus and cytoplasm is not damaged. The macrophages are also quite resistant. The ''light'' reticular cells are the most radiosensitive. The chromatine of their nuclei is dispersed. The mitochondria are imbibed, with a reduced number of cristae. The cytoplasm contains many electron light vesicles, different in size. The changes in the processes of the dendridic cells in the spleen lymph follicles are of particular interest. Compared with the control animals the processes of dendritic reticular cells are markedly reduced. The postirradiation ultrastructural changes of the spleen cells indicate that parallel with the basic factor (the death of a considerable part of the small lymphocytes, precursors of the antibody-synthetizing cells) the reduced antibody-formation is due also to the limited capacity for ''traping'' the antigen on the processes of the dendritic follicular cells and to the reduced capacity of the reticulo-histocytic cells for antigen phagocytosis. The later is determined both by the damage of a considerable part of the phagocytes (radiosensitive ''light'' reticulo-histocytic cells) and by the blocking of the functionally undamaged phagocytes from ingested debris. (K.M.)

  4. Cell surface antigens of radiation leukemia virus-induced BALB/c leukemias defined by syngeneic cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Kaneko, Yukio; Oettgen, H.F.; Obata, Yuichi; Nakayama, Eiichi.

    1989-01-01

    Two cell surface antigens of mouse leukemias were defined by BALB/c cytotoxic T lymphocytes (CTL) generated against syngeneic radiation leukemia virus (RadLV)-induced leukemia, BALBRV1 or BALBRVD. Hyperimmunization of BALB/c mice with irradiated leukemias followed by in vitro sensitization of primed spleen cells resulted in the generation of CTL with high killing activity. The specificity of CTL was examined by direct cytotoxicity assays and competitive inhibition assays. A shared cell surface antigen, designated as BALBRV1 antigen, was detected by BALB/c anti-BALBRV1 CTL. BALBRV1 antigen was expressed not only on RadLV-induced BALB/c leukemias except for BALBRVD, but also on spontaneous or X-ray-induced BALB/c leukemias, chemically-induced leukemias with the H-2 d haplotype and some chemically-induced BALB/c sarcomas. In contrast, a unique cell surface antigen, designated as BALBRVD antigen, was detected by BALB/c anti-BALBRVD CTL. BALBRVD antigen was expressed only on BALBRVD, but not on thirty-nine normal lymphoid or tumor cells. These two antigens could be distinguished from those previously defined on Friend, Moloney, Rauscher or Gross murine leukemia virus (MuLV) leukemias, or MuLV-related antigens. Both cytotoxic responses were blocked by antisera against H-2K d , but not H-2D d . The relationship of BALBRV1 antigen and BALBRVD antigen to endogenous MuLV is discussed with regard to the antigenic distribution on tumor cell lines. (author)

  5. Protective immunization with B16 melanoma induces antibody response and not cytotoxic T cell response

    International Nuclear Information System (INIS)

    Sarzotti, M.; Sriyuktasuth, P.; Klimpel, G.R.; Cerny, J.

    1986-01-01

    C57BL/6 mice immunized with three intraperitoneal injections of syngeneic, irradiated B16 melanoma cells, became resistant to B16 tumor challenge. Immunized mice had high levels of serum antibody against a membrane antigen of B16 cells. The B16 antigen recognized by the anti-B16 sera formed a major band of 90 KD in gel electrophoresis. The anti-B16 antibody was partially protective when mixed with B16 cells and injected into normal recipient mice. Surprisingly, B16 resistance mice were incapable of generating cytotoxic T cells (CTL) specific for the B16 tumor. Both spleen and lymph node cell populations from immunized mice did not generate B16-specific CTL. Allogeneic mice (DBA/2 or C3H) were also unable to generate B16-specific CTL: however, alloreactive CTL produced in these strains of mice by immunization with C57BL/6 lymphocytes, did kill B16 target cells. Interestingly, spleen cells from syngeneic mice immunized with B16 tumor produced 6-fold more interleukin-2 (IL-2) than normal spleen cells, in vitro. These data suggest that immunization with B16 tumor activates a helper subset of T cells (for antibody and IL-2 production) but not the effector CTL response

  6. Spleen vagal denervation inhibits the production of antibodies to circulating antigens.

    Directory of Open Access Journals (Sweden)

    Ruud M Buijs

    Full Text Available BACKGROUND: Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output. METHODOLOGY/PRINCIPAL FINDINGS: This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS, activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA. CONCLUSIONS/SIGNIFICANCE: These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production.

  7. Some Ethical Concerns About Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Zheng, Yue Liang

    2016-10-01

    Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy.

  8. Mechanisms of Virus-Induced Neural Cell Death

    National Research Council Canada - National Science Library

    Tyler, Kenneth

    2002-01-01

    Virtually all known neurotropic viruses are capable of killing infected cells by inducing a specific pattern of cell death known as apoptosis, yet the mechanism by which this occurs and its relevance...

  9. Qidantongmai Protects Endothelial Cells Against Hypoxia-Induced ...

    African Journals Online (AJOL)

    induced damage. The ability of QDTM to modulate the serum VEGF-A level may play an important role in its effects on endothelial cells. Key words: Traditional Chinese Medicine, human umbilical vein endothelial cells, hypoxia, VEGF ...

  10. Role of donor lymphoid cells in the transfer of allograft tolerance

    International Nuclear Information System (INIS)

    Pierce, G.E.; Watts, L.M.

    1985-01-01

    Tolerance to murine skin allografts across a MHC disparity was induced by conditioning primary hosts with sublethal fractionated total-body irradiation (FTBI) and transfusion of allogeneic bone marrow (BM). Tolerance could be adoptively transferred to secondary hosts conditioned by FTBI with infusion of spleen cells from hosts bearing intact skin allografts greater than 60 days. Tolerance could not be transferred by tolerant host spleen (THS) preparations from which cells of the donor genotype had been deleted by cytotoxic alloantisera. Deletion of host genotype cells, however, did not diminish the capability of THS to transfer tolerance. All of the tolerizing activity of THS appeared to reside within cells of the donor genotype. Small numbers of normal donor spleen cells could induce tolerance in FTBI hosts but only at the expense of very high mortality, in contrast to the low mortality observed with tolerizing injections of allogeneic donor cells from THS or injections of normal semiallogeneic F1 hybrid spleen cells. If an active immune response is responsible for tolerance induction/transfer in this model, allogeneic donor lymphoid cells derived from BM, in contrast to donor spleen cells, must be capable of mounting this response without concomitant severe GVHD. In future experiments, cells of donor genotype can be isolated from THS and purified in sufficient numbers to compare their tolerizing efficiency vs. that of normal donor cells, detect possible suppression of normal host cell alloreactivity in vitro and identify the donor cell phenotypes involved

  11. HIV transcription is induced with some forms of cell killing

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Schreck, S.; Chang-Liu, C.-M.; Libertin, C.R.

    1996-01-01

    Using HeLa cells stably transfected with an HIV-LTR-CAT construct', we demonstrated a peak in CAT induction that occurs in viable (but not necessarily cell-division-competent) cells 24 h following exposure to some cell-killing agents. Γ rays were the only cell-killing agent which did not induce HIV transcription; this can be attributed to the fact that γ-ray-induced apoptotic death requires function p53, which is missing in HeLa cells. For all other agents, HIV-LTR induction was dose-dependent and correlated with the amount of cell killing that occurred in the culture

  12. Protective immunity to UV radiation-induced skin tumours induced by skin grafts and epidermal cells

    International Nuclear Information System (INIS)

    Ronald Sluyter; Kylie S Yuen; Gary M Halliday

    2001-01-01

    There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naive recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag-loaded DC to migrate to local lymph nodes. This suggests that cutaneous APC can present tumour Ag to induce protective antitumour immunity. Previously, it has been shown that immunization of mice with MHC class II+ epidermal cells (EC) pulsed with tumour extracts could induce delayed-type hypersensitivity against tumour cells. Here, this same immunization protocol could induce protective immunity against a minimum tumorigenic dose of UVR-induced fibrosarcoma cells, but not higher doses. Epidermal cells obtained from semiallogeneic donors and pulsed with tumour extract could also induce protective immunity. However, presentation of BSA Ag from the culture medium was found to contribute to this result using semiallogeneic EC. The results suggest that LC overlying skin tumours may be able to induce protective immunity to UVR-induced tumours if stimulated to migrate from the skin. Copyright (2001) Australasian Society of Immunology Inc

  13. Radiation leukemia virus and x-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: a growth factor-dependent lymphoma and a growth factor-independent lymphoma

    International Nuclear Information System (INIS)

    Haas, Martin; Rothenberg, Ellen; Bogart, M.H.; Jones, O.W.

    1987-01-01

    Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. The isolation and study of FD-TCL cells was facilitated by their cultivation on stromal hematopoietic monolayers in supplemented ''lymphocyte medium'', until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4-6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype. The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines. (author)

  14. IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance.

    Science.gov (United States)

    Shiokawa, Aya; Tanabe, Kosuke; Tsuji, Noriko M; Sato, Ryuichiro; Hachimura, Satoshi

    2009-06-30

    Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.

  15. Plasmodium chabaudi in mice. Adoptive transfer of immunity with enriched populations of spleen T and B lymphocytes

    International Nuclear Information System (INIS)

    McDonald, V.; Phillips, R.S.

    1978-01-01

    Thymectomized NIH and C57BL mice were more susceptible to Plasmodium chabaudi than controls, indicating a role for T cells in acquired immunity to the parasite. Enriched populations of T and B cells were prepared from the spleens of immune mice using nylon-wool columns, and were adoptively transferred to syngeneic non-irradiated mice or mice irradiated with 600 or 800 rad. Some immunity could usually be transferred with immune T, B and glass-wool (g.w.) filtered spleen cell populations. In the heavily irradiated mice g.w. filtered immune spleen cells gave the best protection and the immune T cells the least. Preliminary attempts to show synergistic activity between immune T and B cells in irradiated mice were not successful. (author)

  16. Properties of murine leukemia viruses produced by leukemic cells established from NIH Swiss mice with radiation-induced leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Okumoto, Masaaki; Nishikawa, Ryosuke; Takamori, Yasuhiko; Iwai, Yoshiaki; Iwai, Mineko [Radiation Center of Osaka Prefecture, Sakai (Japan); Imai, Shunsuke; Morimoto, Junji; Tsubura, Yoshihiko

    1984-06-01

    Three leukemic cell lines, designated NIH-RL1, NIH-RL2 and NFS-RL1, were established from spleen and thymuses of NIH Swiss and NFS mice with radiation-induced leukemia. The culture fluids of these cell lines contained RNA-dependent DNA polymerase (RDDP) activities associated with particles of buoyant density of 1.15-1.17 (g/cm/sup 3/). The divalent cation reqirement of these enzymes was characteristic for that of murine leukemia viruses. In competition radioimmunoassay, a major core protein, p30, was detected in culture fluid of each leukemic cell line. Competition curves of viral p30 produced by these cell lines revealed that these viruses were very similar to those of xenotropic viruses of NZB mice. These viruses were undetectable both by XC plaque assay using SC-1 cells as an indicator cell, and by mink S/sup +/L/sup -/ focus induction assay. These viruses also lacked productive infectivity to mink lung cells (CCL-64), and were nononcogenic in syngeneic mice when the viruses were intrathymically inoculated.

  17. Generation of healthy mice from gene-corrected disease-specific induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Guangming Wu

    2011-07-01

    Full Text Available Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH⁻/⁻ mice as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH⁻/⁻-induced pluripotent stem cells (iPS cells as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH⁻/⁻ iPS cell lines, we aggregated FAH⁻/⁻-iPS cells with tetraploid embryos and obtained entirely FAH⁻/⁻-iPS cell-derived mice that were viable and exhibited the phenotype of the founding FAH⁻/⁻ mice. Then, we transduced FAH cDNA into the FAH⁻/⁻-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell-derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl-1,3-cyclohexanedione. Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models.

  18. [Delayed rupture of the spleen in a multiply injured patient].

    Science.gov (United States)

    Lică, I; Venter, M D; Mehic, R; Marian, R; Ionescu, G

    1997-01-01

    The authors present a case of delayed rupture of the spleen in a polytraumatised patient. This entity was defined as a late occurrence of signs and symptoms attributed to splenic injury not detected by diagnostic computed tomographic scanning during the initial examination. The mechanisms in which the delayed rupture of the spleen occurs are discussed and the conclusion is that the delayed rupture of the spleen represent a real clinical entity.

  19. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Lapidot, T.; Singer, T.S.; Salomon, O.; Terenzi, A.; Schwartz, E.; Reisner, Y.

    1988-01-01

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection

  20. Protein malnutrition induces bone marrow mesenchymal stem cells commitment to adipogenic differentiation leading to hematopoietic failure.

    Science.gov (United States)

    Cunha, Mayara Caldas Ramos; Lima, Fabiana da Silva; Vinolo, Marco Aurélio Ramirez; Hastreiter, Araceli; Curi, Rui; Borelli, Primavera; Fock, Ricardo Ambrósio

    2013-01-01

    Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-γ and C/EBP-α as well as the expression of PPAR-γ and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-γ protein and PPAR-γ mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states.

  1. Protein Malnutrition Induces Bone Marrow Mesenchymal Stem Cells Commitment to Adipogenic Differentiation Leading to Hematopoietic Failure

    Science.gov (United States)

    Cunha, Mayara Caldas Ramos; Lima, Fabiana da Silva; Vinolo, Marco Aurélio Ramirez; Hastreiter, Araceli; Curi, Rui; Borelli, Primavera; Fock, Ricardo Ambrósio

    2013-01-01

    Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-γ and C/EBP-α as well as the expression of PPAR-γ and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-γ protein and PPAR-γ mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states. PMID:23516566

  2. Wandering spleen: a medical enigma, its natural history and rationalization.

    Science.gov (United States)

    Magowska, Anita

    2013-03-01

    Wandering spleen is a rare condition in which the spleen is not located in the left upper quadrant but is found lower in the abdomen or in the pelvic region because of the laxity of the peritoneal attachments. Many patients with wandering spleen are asymptomatic, hence the condition can be discovered only by abdominal examination or at a hospital emergency department if a patient is admitted to hospital because of severe abdominal pain, vomiting or obstipation. This article aims to provide a historical overview of wandering spleen diagnostics and surgical treatment supplemented with an analyses of articles on wandering spleen included in the PubMed database. One of the first clinical descriptions of a wandering spleen was written by Józef Dietl in 1854. The next years of vital importance are 1877 when A. Martin conducted the first splenectomy and in 1895 when Ludwik Rydygier carried out the first splenopexy to immobilize a wandering spleen. Since that time various techniques of splenectomy and splenopexy have been developed. Introducing medical technologies was a watershed in the development and treatment of wandering spleen, which is confirmed by the PubMed database. Despite the increased number of publications medical literature shows that a wandering spleen still remains a misdiagnosed condition, especially among children.

  3. An Unusual Reason for Gastric Variceal Hemorrhage: Wandering Spleen.

    Science.gov (United States)

    Köseoğlu, Hüseyin; Atalay, Roni; Büyükaşık, Naciye Şemnur; Canyiğit, Murat; Özer, Mehmet; Solakoğlu, Tevfik; Akın, Fatma Ebru; Bolat, Aylin Demirezer; Yürekli, Öykü Tayfur; Ersoy, Osman

    2015-12-01

    Wandering spleen is the displacement of the spleen due to the loss or weakening of the ligaments of the spleen and is seen very rarely with an incidence of less than 0.5 %. It can cause portal hypertension, but gastric variceal hemorrhage is a quite rare condition within the spectrum of this uncommon disease. We report a 22-year-old woman with wandering spleen presenting with life-threatening gastric variceal hemorrhage. Her diagnosis was made by computerized tomography. Endoscopic therapy was not adequate to stop the bleeding, and urgent splenectomy was performed. After surgery she has been well with no symptoms until now.

  4. Langerhans cells are required for UVR-induced immunosuppression

    NARCIS (Netherlands)

    Schwarz, Agatha; Noordegraaf, Madelon; Maeda, Akira; Torii, Kan; Clausen, Björn E.; Schwarz, Thomas

    2010-01-01

    Painting of haptens onto UVR-exposed skin does not result in sensitization but induces regulatory T cells (Treg). This was explained by UVR-mediated depletion of Langerhans cells (LCs). Furthermore, migration of UVR-damaged but still viable LCs into lymph nodes appears to be essential to induce

  5. Deep-Sea-Derived Butyrolactone I Suppresses Ovalbumin-Induced Anaphylaxis by Regulating Mast Cell Function in a Murine Model.

    Science.gov (United States)

    Liu, Qing-Mei; Xie, Chun-Lan; Gao, Yuan-Yuan; Liu, Bo; Lin, Wei-Xiang; Liu, Hong; Cao, Min-Jie; Su, Wen-Jin; Yang, Xian-Wen; Liu, Guang-Ming

    2018-05-22

    Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.

  6. Alpha Particles Induce Autophagy in Multiple Myeloma Cells.

    Science.gov (United States)

    Gorin, Jean-Baptiste; Gouard, Sébastien; Ménager, Jérémie; Morgenstern, Alfred; Bruchertseifer, Frank; Faivre-Chauvet, Alain; Guilloux, Yannick; Chérel, Michel; Davodeau, François; Gaschet, Joëlle

    2015-01-01

    Radiation emitted by the radionuclides in radioimmunotherapy (RIT) approaches induce direct killing of the targeted cells as well as indirect killing through the bystander effect. Our research group is dedicated to the development of α-RIT, i.e., RIT using α-particles especially for the treatment of multiple myeloma (MM). γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by (213)Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of (213)Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation. Murine 5T33 and human LP-1 MM cell lines were used to study the effects of such α-particles. We first examined the effects of (213)Bi on proliferation rate, double-strand DNA breaks, cell cycle, and cell death. Then, we investigated autophagy after (213)Bi irradiation. Finally, a coculture of dendritic cells (DCs) with irradiated tumor cells or their culture media was performed to test whether it would induce DC activation. We showed that (213)Bi induces DNA double-strand breaks, cell cycle arrest, and autophagy in both cell lines, but we detected only slight levels of early apoptosis within the 120 h following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented (213)Bi-induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s); however, no increase in membrane or extracellular expression of danger-associated molecular patterns was observed after irradiation. This study demonstrates that (213)Bi induces mainly necrosis in MM cells, low levels of apoptosis, and autophagy that might be involved in tumor cell death.

  7. Alpha-particles induce autophagy in multiple myeloma cells

    Directory of Open Access Journals (Sweden)

    Joelle Marcelle Gaschet

    2015-10-01

    Full Text Available Objectives: Radiations emitted by the radionuclides in radioimmunotherapy (RIT approaches induce direct killing of the targeted cells as well as indirect killing through bystander effect. Our research group is dedicated to the development of α-RIT, i.e RIT using α-particles especially for the treatment of multiple myeloma (MM. γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by 213Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of 213Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation.Methods: Murine 5T33 and human LP-1 multiple myeloma (MM cell lines were used to study the effects of such α-particles. We first examined the effects of 213Bi on proliferation rate, double strand DNA breaks, cell cycle and cell death. Then, we investigated autophagy after 213Bi irradiation. Finally, a co-culture of dendritic cells (DC with irradiated tumour cells or their culture media was performed to test whether it would induce DC activation.Results: We showed that 213Bi induces DNA double strand breaks, cell cycle arrest and autophagy in both cell lines but we detected only slight levels of early apoptosis within the 120 hours following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented 213Bi induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s, however no increase in membrane or extracellular expression of danger associated molecular patterns (DAMPs was observed after irradiation.Conclusion: This study demonstrates that 213Bi induces mainly necrosis in MM cells, low levels of apoptosis and also autophagy that might be involved in tumor cell death.

  8. Morphogenesis of early stages of hemopoiesis recovery in the spleen in irradiated mice after the bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Nezdatnii, M M; Zaitseva, K K [Voenno-Morskaya Akademiya, Leningrad (USSR)

    1975-12-01

    The study was made of the early stages of exogenous hemopoietik colonies formation. The cell composition of the spleen red pulp in irradiated recipients was subjected to quantitative morphological analysis, and the number of colony-forming units (CFU) in the spleen was counted. The BALB/C mice were subjected to single irradiation with gamma-rays (dose: 75OR) on a cobalt (/sup 60/Co) installation. The results of the morphological analysis of the cell composition of the spleen red pulp in irradiated recipients, of the bone marrow, and of the CFU kinetics afforded the possibility to establish the following three stages in the spleen during the early processes of hemopoietic regeneration: systemic activation of reticular cells in the spleen red pulp; formation of microcolonies from non-differentiated blastic cells (n.b.c.); and appearance of hematologically differentiated cells (h.d.c.) and CFU proliferation. The rapid growth of the number of n.b.c. on the second, third and fourth days after transplantation of the bone marrow involved weakly pronounced mitotic activity. This is considered to bndirect indication of transformation of activated reticular cells in n.b.c.

  9. Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis

    Science.gov (United States)

    Kremer, Kimberly N.; Dudakovic, Amel; McGee-Lawrence, Meghan E.; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.

    2014-01-01

    The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment. PMID:24851270

  10. Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Yuan-Chang Chang

    2011-01-01

    Full Text Available Emodin is one of major compounds in rhubarb (Rheum palmatum L., a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3 and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca2+ and reduced the level of ΔΨm by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

  11. Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells.

    Science.gov (United States)

    Vieira Torquato, Heron F; Ribeiro-Filho, Antonio C; Buri, Marcus V; Araújo Júnior, Roberto T; Pimenta, Renata; de Oliveira, José Salvador R; Filho, Valdir C; Macho, Antonio; Paredes-Gamero, Edgar J; de Oliveira Martins, Domingos T

    2017-04-01

    Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin + ) and leukemia stem cell population (CD34 + CD38 - Lin -/low ). Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at G 0 /G 1 (7μM) and G 2 (45μM) evidenced by DNA content, BrdU incorporation and cyclin B1/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Polyphosphate induces matrix metalloproteinase-3-mediated proliferation of odontoblast-like cells derived from induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Yamaguchi, Hideyuki; Hiyama, Taiki; Kawai, Rie [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan)

    2015-05-01

    Inorganic polyphosphate [Poly(P)] may represent a physiological source of phosphate and has the ability to induce bone differentiation in osteoblasts. We previously reported that cytokine-induced matrix metalloproteinase (MMP)-3 accelerates the proliferation of purified odontoblast-like cells. In this study, MMP-3 small interfering RNA (siRNA) was transfected into odontoblast-like cells derived from induced pluripotent stem cells to investigate whether MMP-3 activity is induced by Poly(P) and/or is associated with cell proliferation and differentiation into odontoblast-like cells. Treatment with Poly(P) led to an increase in both cell proliferation and additional odontoblastic differentiation. Poly(P)-treated cells showed a small but significant increase in dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) mRNA expression, which are markers of mature odontoblasts. The cells also acquired additional odontoblast-specific properties including adoption of an odontoblastic phenotype typified by high alkaline phosphatase (ALP) activity and a calcification capacity. In addition, Poly(P) induced expression of MMP-3 mRNA and protein, and increased MMP-3 activity. MMP-3 siRNA-mediated disruption of the expression of these effectors potently suppressed the expression of odontoblastic biomarkers ALP, DSPP, and DMP-1, and blocked calcification. Interestingly, upon siRNA-mediated silencing of MMP-3, we noted a potent and significant decrease in cell proliferation. Using specific siRNAs, we revealed that a unique signaling cascade, Poly(P)→MMP-3→DSPP and/or DMP-1, was intimately involved in the proliferation of odontoblast-like cells. - Highlights: • Polyphosphate increases proliferation of iPS cell-derived odontoblast-like cells. • Polyphosphate-induced MMP-3 results in an increase of cell proliferation. • Induced cell proliferation involves MMP-3, DSPP, and/or DMP-1 sequentially. • Induced MMP-3 also results in an increase of odontoblastic

  13. Cytotoxic Capacity of IL-15-Stimulated Cytokine-Induced Killer Cells Against Human Acute Myeloid Leukemia and Rhabdomyosarcoma in Humanized Preclinical Mouse Models

    Energy Technology Data Exchange (ETDEWEB)

    Rettinger, Eva; Meyer, Vida; Kreyenberg, Hermann [Department of Pediatric Hematology, Oncology and Hemostaseology, University Children’s Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany); Volk, Andreas [Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt/Main (Germany); Kuçi, Selim; Willasch, Andre [Department of Pediatric Hematology, Oncology and Hemostaseology, University Children’s Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany); Koscielniak, Ewa [Department of Pediatric Oncology and Hematology, Olgahospital Stuttgart, Stuttgart (Germany); Fulda, Simone [Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany); Wels, Winfried S. [Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt/Main (Germany); Boenig, Halvard [Institute for Transfusion Medicine and Immunohematology, Goethe-University Frankfurt/Main, Division for Cell Processing, German Red Cross Blood Donor Service Baden-Württemberg-Hessen, Frankfurt/Main (Germany); Klingebiel, Thomas; Bader, Peter, E-mail: eva.rettinger@kgu.de, E-mail: peter.bader@kgu.de [Department of Pediatric Hematology, Oncology and Hemostaseology, University Children’s Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main (Germany)

    2012-04-09

    Allogeneic stem cell transplantation (allo-SCT) has become an important treatment modality for patients with high-risk acute myeloid leukemia (AML) and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD) status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions based on MRD status using IL-15-expanded cytokine-induced killer (CIK) cells may prevent relapse without causing graft-versus-host-disease (GvHD). To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL-2Rγc{sup −}, NSG) were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS) cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow followed by liver, lung, spleen, peripheral blood (PB), and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at equal amounts were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells 250 times more CIK than THP-1 cells were needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliable 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells have potent cytotoxic capacity

  14. Glucocorticoid-induced TNF receptor family related protein ligand [GITR-L] is requisite for optimal functioning of regulatory CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Gongxian eLiao

    2014-02-01

    Full Text Available Glucocorticoid-Induced Tumor necrosis factor Receptor family-related protein (GITR, TNFRSF18, CD357 is constitutively expressed on regulatory T cells (Tregs and is inducible on effector T cells (Teffs. In this report, we examine the role of GITR-Ligand (GITR-L, which is expressed by antigen presenting cells, on the development and expansion of Tregs. We found that GITR-L is dispensable for the development of naturally occurring FoxP3+ Treg cells in the thymus. However, the expansion of Treg in GITR-L-/- mice is impaired after injection of the dendritic cells (DCs inducing factor Flt3 ligand. Furthermore, DCs from the liver of GITR-L-/- mice were less efficient in inducing proliferation of antigen-specific Treg cells in vitro than the same cells from WT littermates. Upon gene transfer of ovalbumin into hepatocytes of GITR-L-/- FoxP3(GFP reporter mice using adeno-associated virus (AAV8-OVA the number of antigen-specific Treg in liver and spleen is reduced. The reduced number of Tregs resulted in an increase in the number of ovalbumin specific CD8+ T effector cells. This is highly significant because proliferation of antigen specific CD8+ cells itself is dependent on the presence of GITR-L, as shown by in vitro experiments and by adoptive transfers into GITR-L-/-Rag-/- and Rag-/- mice that had received AAV8-OVA. Surprisingly, administering αCD3 significantly reduced the numbers of FoxP3+ Treg cells in the liver and spleen of GITR-L-/- but not WT mice. Because soluble Fc-GITR-L partially rescues αCD3 induced in vitro depletion of the CD103+ subset of FoxP3+CD4+ Treg cells, we conclude that expression of GITR-L by antigen presenting cells is requisite for optimal Treg-mediated regulation of immune responses including those in response during gene transfer.

  15. Porcine circovirus-2 capsid protein induces cell death in PK15 cells

    Energy Technology Data Exchange (ETDEWEB)

    Walia, Rupali; Dardari, Rkia, E-mail: rdardari@ucalgary.ca; Chaiyakul, Mark; Czub, Markus

    2014-11-15

    Studies have shown that Porcine circovirus (PCV)-2 induces apoptosis in PK15 cells. Here we report that cell death is induced in PCV2b-infected PK15 cells that express Capsid (Cap) protein and this effect is enhanced in interferon gamma (IFN-γ)-treated cells. We further show that transient PCV2a and 2b-Cap protein expression induces cell death in PK15 cells at rate similar to PCV2 infection, regardless of Cap protein localization. These data suggest that Cap protein may have the capacity to trigger different signaling pathways involved in cell death. Although further investigation is needed to gain deeper insights into the nature of the pathways involved in Cap-induced cell death, this study provides evidence that PCV2-induced cell death in kidney epithelial PK15 cells can be mapped to the Cap protein and establishes the need for future research regarding the role of Cap-induced cell death in PCV2 pathogenesis. - Highlights: • IFN-γ enhances PCV2 replication that leads to cell death in PK15 cells. • IFN-γ enhances nuclear localization of the PCV2 Capsid protein. • Transient PCV2a and 2b-Capsid protein expression induces cell death. • Cell death is not dictated by specific Capsid protein sub-localization.

  16. Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

    Science.gov (United States)

    Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

    2017-07-01

    The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

  17. Chicken Induced Pluripotent Stem Cells: Establishment and Characterization.

    Science.gov (United States)

    Fuet, Aurelie; Pain, Bertrand

    2017-01-01

    In mammals, the introduction of the OSKM (Oct4, Sox2, Klf4, and c-Myc) genes into somatic cells has allowed generating induced pluripotent stem (iPS) cells. So far, this process has been only clearly demonstrated in mammals. Here, using chicken as an avian model, we describe a set of protocols allowing the establishment, characterization, maintenance, differentiation, and injection of putative reprogrammed chicken Induced Pluripotent Stem (iPS) cells.

  18. Aspartame-induced apoptosis in PC12 cells

    OpenAIRE

    Horio, Yukari; Sun, Yongkun; Liu, Chuang; Saito, Takeshi; Kurasaki, Masaaki

    2014-01-01

    Aspartame is an artificial sweetner added to many low-calorie foods. The safety of aspartame remains controversial even though there are many studies on its risks. In this study, to understand the physiological effects of trace amounts of artificial sweetners on cells, the effects of aspartame on apoptosis were investigated using a PC12 cell system. In addition, the mechanism of apoptosis induced by aspartame in PC12 cells and effects on apoptotic factors such as cytochrome c, apoptosis-induc...

  19. Oxidative Stress Induces Senescence in Cultured RPE Cells.

    Science.gov (United States)

    Aryan, Nona; Betts-Obregon, Brandi S; Perry, George; Tsin, Andrew T

    2016-01-01

    The aim of this research is to determine whether oxidative stress induces cellular senescence in human retinal pigment epithelial cells. Cultured ARPE19 cells were subjected to different concentrations of hydrogen peroxide to induce oxidative stress. Cells were seeded into 24-well plates with hydrogen peroxide added to cell medium and incubated at 37°C + 5% CO2 for a 90-minute period [at 0, 300, 400 and 800 micromolar (MCM) hydrogen peroxide]. The number of viable ARPE19 cells were recorded using the Trypan Blue Dye Exclusion Method and cell senescence was measured by positive staining for senescence-associated beta-galactosidase (SA-beta-Gal) protein. Without hydrogen peroxide treatment, the number of viable ARPE19 cells increased significantly from 50,000 cells/well to 197,000 within 72 hours. Treatment with hydrogen peroxide reduced this level of cell proliferation significantly (to 52,167 cells at 400 MCM; to 49,263 cells at 800 MCM). Meanwhile, cells with a high level of positive senescence-indicator SA-Beta-Gal-positive staining was induced by hydrogen peroxide treatment (from a baseline level of 12% to 80% at 400 MCM and at 800 MCM). Our data suggests that oxidative stress from hydrogen peroxide treatment inhibited ARPE19 cell proliferation and induced cellular senescence.

  20. Modulation of Host miRNAs Transcriptome in Lung and Spleen of Peste des Petits Ruminants Virus Infected Sheep and Goats

    Directory of Open Access Journals (Sweden)

    Aruna Pandey

    2017-06-01

    Full Text Available Peste des petits ruminants (PPR is one of the highly contagious viral disease, characterized by fever, sore mouth, conjunctivitis, gastroenteritis, and pneumonia, primarily affecting sheep and goats. Reports suggested variable host response in goats and sheep and this host response vis-a-vis the expression of microRNAs (miRNAs has not been investigated. Here, miRNAs were sequenced and proteomics data were generated to identify the role of differentially expressed miRNA (DEmiRNA in PPR virus (PPRV infected lung and spleen tissues of sheep and goats. In lungs, 67 and 37 DEmiRNAs have been identified in goats and sheep, respectively. Similarly, in spleen, 50 and 56 DEmiRNAs were identified in goats and sheep, respectively. A total of 20 and 11 miRNAs were found to be common differentially expressed in both the species in PPRV infected spleen and lung, respectively. Six DEmiRNAs—miR-21-3p, miR-1246, miR-27a-5p, miR-760-3p, miR-320a, and miR-363 were selected based on their role in viral infections, apoptosis, and fold change. The target prediction analysis of these six selected DEmiRNAs from the proteome data generated, revealed involvement of more number of genes in lung and spleen of goats than in sheep. On gene ontology analysis of host target genes these DEmiRNAs were found to regulate several immune response signaling pathways. It was observed that the pathways viz. T cell receptor signaling, Rap1 signaling, Toll-like receptor signaling, and B cell receptor signaling governed by DEmiRNAs were more perturbed in goats than in sheep. The data suggests that PPRV-induced miR-21-3p, miR-320a, and miR-363 might act cooperatively to enhance viral pathogenesis in the lung and spleen of sheep by downregulating several immune response genes. The study gives an important insight into the molecular pathogenesis of PPR by identifying that the PPRV—Izatnagar/94 isolate elicits a strong host response in goats than in sheep.

  1. Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models

    Directory of Open Access Journals (Sweden)

    Eva eRettinger

    2012-04-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT has become an important treatment modality for patients with high risk acute myeloid leukemia (AML and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions (DLI based on MRD status using IL-15-expanded cytokine-induced killer (CIK cells may prevent relapse without causing graft-versus-host-disease (GvHD. To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL2Rγc-, NSG were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction (qPCR for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow (BM followed by liver, lung, spleen, peripheral blood (PB, and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at an effector to target cell (E:T ratio of 1:1 were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells an E:T ratio of 250:1 was needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliably 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells

  2. Study of chicken liver and spleen by Moessbauer spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Division of Applied Biophysics, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation); Malakheeva, L. I. [Simbio Holding, Science Consultation Department (Russian Federation); Prokopenko, P. G. [Russian State Medical University, Faculty of Biochemistry (Russian Federation)

    2005-09-15

    A preliminary study of purified normal human liver ferritin, normal chicken liver and spleen tissues in lyophilized form showed differences in room temperature Moessbauer hyperfine parameters. An additional study of liver and spleen tissues with lower iron content from chicken with lymphoid leukemia indicated small differences between the quadrupole splittings in these samples compared with those in normal tissues.

  3. Study of chicken liver and spleen by Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Malakheeva, L. I.; Prokopenko, P. G.

    2005-01-01

    A preliminary study of purified normal human liver ferritin, normal chicken liver and spleen tissues in lyophilized form showed differences in room temperature Moessbauer hyperfine parameters. An additional study of liver and spleen tissues with lower iron content from chicken with lymphoid leukemia indicated small differences between the quadrupole splittings in these samples compared with those in normal tissues.

  4. Evolution of the CT imaging findings of accessory spleen infarction

    International Nuclear Information System (INIS)

    Mendi, Resham; Abramson, Lisa P.; Pillai, Srikumar B.; Rigsby, Cynthia K.

    2006-01-01

    We report the case of a 12-year-old girl presenting with multiple episodes of left upper-quadrant pain caused by torsion of an accessory spleen. We present the CT findings of progression of accessory spleen infarction over the course of 7 days. (orig.)

  5. The wandering spleen: CT findings and possible pitfalls in diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Ben Ely, A.; Zissin, R.; Copel, L.; Vasserman, M.; Hertz, M.; Gottlieb, P.; Gayer, G

    2006-11-15

    Aim: To report the CT features of wandering spleen, a rare condition which can be incidentally detected as an abdominal or pelvic mass or can present with torsion, causing an acute abdomen. Materials and methods: The CT studies of seven patients, two children and five adults, with wandering spleen were reviewed. CT was performed urgently in three patients for acute abdomen, and electively in four. Results: CT findings of wandering spleen included absence of the spleen in its normal position and a mass located elsewhere in the abdomen or pelvis, i.e. an ectopic spleen, enhancing homogeneously in four cases and failing partially or completely to enhance in the other three, indicating infarction. A 'whirl' appearance representing the twisted splenic pedicle was seen in the three cases with torsion. Urgent splenectomy confirmed infarction secondary to torsion. Conclusion: The possible diagnosis of wandering spleen should be kept in mind when CT shows the spleen to be absent from its usual position and a mass is found elsewhere in the abdomen or pelvis. When, in addition, a 'whirl' or partial or no enhancement of this mass are seen in a case presenting with acute abdomen, torsion of a wandering spleen is a likely diagnosis.

  6. Use of nucleotides in weanling rats with diarrhea induced by a lactose overload: effect on the evolution of diarrhea and weight and on the histopathology of intestine, liver and spleen

    Directory of Open Access Journals (Sweden)

    Norton R.

    2001-01-01

    Full Text Available Until recently, dietary sources of nucleotides were thought not to be essential for good nutrition. Certain states with higher metabolic demands may require larger amounts that cannot be provided by endogenous production. The objective of the present study was to determine the action of nucleotides on the recovery from lactose-induced diarrhea in weaned rats. Thirty-six weanling Fisher rats were divided into two groups. Group 1 received a standard diet and group 2 received a diet containing lactose in place of starch. On the 10th day, six animals per group were sacrificed for histopathological evaluation. The remaining animals were divided into two other subgroups, each with 6 animals, receiving a control diet, a control diet with nucleotides (0.05% adenosine monophosphate, 0.05% guanosine monophosphate, 0.05% cytidine monophosphate, 0.05% uridine monophosphate and 0.05% inosine monophosphate, a diet with lactose, and a diet with lactose and nucleotides. On the 32nd day of the experiment all animals were sacrificed. Animals with diarrhea weighed less than animals without diarrhea. The introduction of nucleotides did not lead to weight gain. Mean diet consumption was lower in the group that continued to ingest lactose, with the group receiving lactose plus nucleotides showing a lower mean consumption. Animals receiving lactose had inflammatory reaction and deposits of periodic acid-Schiff-positive material in intestinal, hepatic and splenic tissues. The introduction of nucleotides led to an improvement of the intestinal inflammatory reaction. In lactose-induced diarrhea, when the stimulus is maintained - lactose overload - the nucleotides have a limited action on the weight gain and on recovery of intestinal morphology, although they have a protective effect on hepatic injury and improve the inflammatory response.

  7. Hyperthermia: an effective strategy to induce apoptosis in cancer cells.

    Science.gov (United States)

    Ahmed, Kanwal; Tabuchi, Yoshiaki; Kondo, Takashi

    2015-11-01

    Heat has been used as a medicinal and healing modality throughout human history. The combination of hyperthermia (HT) with radiation and anticancer agents has been used clinically and has shown positive results to a certain extent. However, the clinical results of HT treatment alone have been only partially satisfactory. Cell death following HT treatment is a function of both temperature and treatment duration. HT induces cancer cell death through apoptosis; the degree of apoptosis and the apoptotic pathway vary in different cancer cell types. HT-induced reactive oxygen species production are responsible for apoptosis in various cell types. However, the underlying mechanism of signal transduction and the genes related to this process still need to be elucidated. In this review, we summarize the molecular mechanism of apoptosis induced by HT, enhancement of heat-induced apoptosis, and the genetic network involved in HT-induced apoptosis.

  8. Sorafenib-induced defective autophagy promotes cell death by necroptosis.

    Science.gov (United States)

    Kharaziha, Pedram; Chioureas, Dimitris; Baltatzis, George; Fonseca, Pedro; Rodriguez, Patricia; Gogvadze, Vladimir; Lennartsson, Lena; Björklund, Ann-Charlotte; Zhivotovsky, Boris; Grandér, Dan; Egevad, Lars; Nilsson, Sten; Panaretakis, Theocharis

    2015-11-10

    Autophagy is one of the main cytoprotective mechanisms that cancer cells deploy to withstand the cytotoxic stress and survive the lethal damage induced by anti-cancer drugs. However, under specific conditions, autophagy may, directly or indirectly, induce cell death. In our study, treatment of the Atg5-deficient DU145 prostate cancer cells, with the multi-tyrosine kinase inhibitor, sorafenib, induces mitochondrial damage, autophagy and cell death. Molecular inhibition of autophagy by silencing ULK1 and Beclin1 rescues DU145 cells from cell death indicating that, in this setting, autophagy promotes cell death. Re-expression of Atg5 restores the lipidation of LC3 and rescues DU145 and MEF atg5-/- cells from sorafenib-induced cell death. Despite the lack of Atg5 expression and LC3 lipidation, DU145 cells form autophagosomes as demonstrated by transmission and immuno-electron microscopy, and the formation of LC3 positive foci. However, the lack of cellular content in the autophagosomes, the accumulation of long-lived proteins, the presence of GFP-RFP-LC3 positive foci and the accumulated p62 protein levels indicate that these autophagosomes may not be fully functional. DU145 cells treated with sorafenib undergo a caspase-independent cell death that is inhibited by the RIPK1 inhibitor, necrostatin-1. Furthermore, treatment with sorafenib induces the interaction of RIPK1 with p62, as demonstrated by immunoprecipitation and a proximity ligation assay. Silencing of p62 decreases the RIPK1 protein levels and renders necrostatin-1 ineffective in blocking sorafenib-induced cell death. In summary, the formation of Atg5-deficient autophagosomes in response to sorafenib promotes the interaction of p62 with RIPK leading to cell death by necroptosis.

  9. Hexavalent chromium induces chromosome instability in human urothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wise, Sandra S. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Liou, Louis [Department of Pathology, Boston University School of Medicine, 670 Albany St., Boston, MA 02118 (United States); Adam, Rosalyn M. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Wise, John Pierce Sr., E-mail: john.wise@louisville.edu [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States)

    2016-04-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.

  10. Characterization and comparison of osteoblasts derived from mouse embryonic stem cells and induced pluripotent stem cells

    NARCIS (Netherlands)

    Ma, Ming San; Kannan, Vishnu; de Vries, Anneriek E; Czepiel, Marcin; Wesseling, Evelyn; Balasubramaniyan, Veerakumar; Kuijer, Roelof; Vissink, Arjan; Copray, Sjef; Raghoebar, Gerry

    New developments in stem cell biology offer alternatives for the reconstruction of critical-sized bone defects. One of these developments is the use of induced pluripotent stem (iPS) cells. These stem cells are similar to embryonic stem (ES) cells, but can be generated from adult somatic cells and

  11. ENDOGENOUS PYROGEN RELEASE FROM RABBIT BLOOD CELLS INCUBATED IN VITRO WITH PARAINFLUENZA VIRUS.

    Science.gov (United States)

    ATKINS, E; CRONIN, M; ISACSON, P

    1964-12-11

    Rabbit blood cells incubated in vitro with purified parainfluenza-5 virus (DA strain) released a rapidly acting pyrogen. Spleen and lymph node cells were inactive. The pyrogen resembled in behavior a pyrogen extracted from granulocytic exudates. Similar cells in the blood are believed to be activated by virus in vivo to produce the circulating endogenous pyrogen that mediates virus-induced fever.

  12. Study of ultrasonic imagine of spleen in patients with leukemia

    International Nuclear Information System (INIS)

    Zheng Hui; Zhou Chunyan; Jiang Ju; Luo Liying; Huang Yanhong

    2011-01-01

    To investigate spleen ultrasonic imagine in patients with leukemia and to provide basis information for preventing and treat disease,the spleens imaging of 158 patients with leukemia were detected by B mode ultrasonicgraphy and the data of clinical medical examination were analyzed.The results showed that the spleens' ultrasonic imagine of patients with leukemia were not related to the degree of anemia.The ultrasonic imagines of spleen in patients with chronic leukemia were different to the other kinds of leukemia.The ultrasonic imagine of spleens in leukemia patients are related to types and development of leukemia.The B-ultrasound screening should be used to help clinical diagnosis and treatment of patients with leukemia. (authors)

  13. Arsenic exposure induces the Warburg effect in cultured human cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

  14. Arsenic exposure induces the Warburg effect in cultured human cells

    International Nuclear Information System (INIS)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

    2013-01-01

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect

  15. A cluster of coregulated genes determines TGF-β–induced regulatory T-cell (Treg) dysfunction in NOD mice

    Science.gov (United States)

    D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe

    2011-01-01

    Foxp3+ regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4+ T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility. PMID:21543717

  16. A cluster of coregulated genes determines TGF-beta-induced regulatory T-cell (Treg) dysfunction in NOD mice.

    Science.gov (United States)

    D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A; Mathis, Diane; Benoist, Christophe

    2011-05-24

    Foxp3(+) regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4(+) T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility.

  17. Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study

    OpenAIRE

    Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

    2016-01-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis act...

  18. Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses

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    Andoh Y

    2013-01-01

    Full Text Available Yoshiaki Andoh,1,2 Naohiko Makino,2 Mitsunori Yamakawa11Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanBackground: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL and CD4+CD25high regulatory T-cells (Tregs among dendritic cells (DCs fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs, were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.Results: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1 was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.Conclusion: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs

  19. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    International Nuclear Information System (INIS)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi

    2015-01-01

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells

  20. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Fujisaki, Hitomi; Hattori, Shunji [Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017 (Japan); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Ikejima, Takashi, E-mail: ikejimat@vip.sina.com [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)

    2015-02-20

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.

  1. Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells

    Directory of Open Access Journals (Sweden)

    Yonghae Son

    2016-01-01

    Full Text Available Oxysterol like 27-hydroxycholesterol (27OHChol has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined whether dexamethasone (Dx affects 27OHChol-induced differentiation using THP-1 cells. Treatment of monocytic cells with Dx resulted in almost complete inhibition of transcription and surface expression of CD80, CD83, and CD88 induced by 27OHChol. Elevated surface levels of MHC class I and II molecules induced by 27OHChol were reduced to basal levels by treatment with Dx. A decreased endocytosis ability caused by 27OHChol was recovered by Dx. We also examined effects of Dx on expression of CD molecules involved in atherosclerosis. Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx. These results indicate that Dx inhibits 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules whose levels are associated with atherosclerosis. In addition, we examined phosphorylation of AKT induced by 27OHChol and effect of Dx, where cotreatment with Dx inhibited the phosphorylation of AKT. The current study reports that Dx regulates oxysterol-mediated dendritic cell differentiation of monocytic cells.

  2. Immobilization of yeast cells by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Fujimura, T.; Kaetsu, I.

    1982-01-01

    Radiation-induced polymerization method was applied to the immobilization of yeast cells. The effects of irradiation, cooling and monomer, which are neccessary for polymerization, were recovered completely by subsequent aerobical incubation of yeast cells. The ethanol productive in immobilized yeast cells increased with the increase of aerobical incubation period. The growth of yeast cells in immobilized yeast cells was indicated. The maximum ethanol productivity in immobilized yeast cell system was around three times as much as that in free yeast cell system. (orig.)

  3. Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells.

    Science.gov (United States)

    Biswas, Dhruba; Jiang, Peng

    2016-02-06

    The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming.

  4. Glucocorticoid cell reception in mice of different strains with natural killer cell activity depressed during immobilization stress

    International Nuclear Information System (INIS)

    Lyashko, V.N.; Sukhikh, G.T.

    1987-01-01

    The authors study differences in stress-induced depression of natural killer cell activity in mice of different inbred lines, depending on parameters of glucocorticoid binding with glucorticoid receptors of spleen cells and on the hormonal status of the animals. In determining the parameters of glucocorticoid binding on intact splenocytes, aliquots of a suspension of washed splenocytes were incubated with tritium-labeled dexamethasone

  5. Apoptosis in T lymphocytes from spleen tissue and peripheral blood of L. (L.) chagasi naturally infected dogs.

    Science.gov (United States)

    de Lima, Valéria Marçal Felix; Fattori, Karina Reinaldo; de Souza, Fausto; Eugênio, Flavia Rezende; dos Santos, Paulo Sérgio Patto; Rozza, Daniele Bernadete; Machado, Gisele Fabrino

    2012-03-23

    Dogs are the main domestic reservoirs of L. (L.) chagasi. Once in the vertebrate host, the parasite may cause visceral leishmaniasis, which can also be transmitted to humans. Infected symptomatic dogs show disorganization in the white pulp in spleen tissue and a reduction in T lymphocytes in peripheral blood. To investigate whether apoptosis is involved in white pulp disorganization and diminished T cell counts in peripheral blood, apoptotic T cells from the spleen and peripheral blood of dogs naturally infected with L. (L.) chagasi and presenting clinical manifestations were quantified and compared with healthy dogs. Thirteen symptomatic adult dogs infected by L. (L.) chagasi and six healthy dogs from a nonendemic area (controls) were included in the study. Samples from spleen and peripheral blood were used to quantify apoptosis in CD3 lymphocytes by flow cytometry using Anexin V and Multicaspase kits; the results were compared using the Mann Whitney test. The percentage of total T cells was lower in Leishmania infected dogs compared to healthy controls (Pspleen were higher in infected dogs than in controls (Pspleen white pulp and the percentage of apoptosis in the spleen. A significant effect on the level of white pulp morphological disorganization and percentage of apoptosis in spleen T cells was observed (F=20.45; P=0.0014). These data suggest that apoptosis is an important for the immunopathogenesis of canine visceral leishmaniasis. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Src Induces Podoplanin Expression to Promote Cell Migration*

    Science.gov (United States)

    Shen, Yongquan; Chen, Chen-Shan; Ichikawa, Hitoshi; Goldberg, Gary S.

    2010-01-01

    Nontransformed cells can force tumor cells to assume a normal morphology and phenotype by the process of contact normalization. Transformed cells must escape this process to become invasive and malignant. However, mechanisms underlying contact normalization have not been elucidated. Here, we have identified genes that are affected by contact normalization of Src-transformed cells. Tumor cells must migrate to become invasive and malignant. Src must phosphorylate the adaptor protein Cas (Crk-associated substrate) to promote tumor cell motility. We report here that Src utilizes Cas to induce podoplanin (Pdpn) expression to promote tumor cell migration. Pdpn is a membrane-bound extracellular glycoprotein that associates with endogenous ligands to promote tumor cell migration leading to cancer invasion and metastasis. In fact, Pdpn expression accounted for a major part of the increased migration seen in Src-transformed cells. Moreover, nontransformed cells suppressed Pdpn expression in adjacent Src-transformed cells. Of >39,000 genes, Pdpn was one of only 23 genes found to be induced by transforming Src activity and suppressed by contact normalization of Src-transformed cells. In addition, we found 16 genes suppressed by Src and induced by contact normalization. These genes encode growth factor receptors, adaptor proteins, and products that have not yet been annotated and may play important roles in tumor cell growth and migration. PMID:20123990

  7. Brucella abortus-infected B cells induce osteoclastogenesis.

    Science.gov (United States)

    Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2016-09-01

    Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. Radiation induced processes in moss cells

    International Nuclear Information System (INIS)

    Doehren, R. v.

    1975-01-01

    The moss F.h. shows apical growth in the protonema cells which spread radially from the spor. Every apical daughter cell during the state of 'Caulonema' and just before in the state of 'Caulonema Primanen' initiates cell division as soon as more than twice the length of the mother cell is reached. All this allows to follow radiation effects in single cells conveniently. UV irradiation on the range of 254 nm and 280 nm delivered at different parts of the cell area delays cell division markedly may suppress it, and is able to stop the process of growing in relation to the delivered dose and to the irradiated area as well. In case of irradiation of the area next to where the membrane is just being formed - that is to say next to the phragmoplast - the new membrane will be wrongly oriented. In particular giant cells are occurring in the case of nucleus irradiation during early prophase. (orig./GSE) [de

  9. [Study on thaspine in inducing apoptosis of A549 cell].

    Science.gov (United States)

    Zhang, Yan-min; He, Lang-chong

    2007-04-01

    To investigate the effect of thaspine on the cellular proliferation, apoptosis and cell cycle in A549 cell line. A549 cell was cultured with different concentrations of thaspine. Cellular proliferation was detected with MTT, apoptosis and cell cycle were checked with Flow Cytometer, and change of microstructure was observed by transmission electron microscope. Thaspine could inhibit the proliferation and induce apoptosis of A549 cell in a time-dose dependent manner. Cell cycle was significantly stopped at the S phase by thaspine with FCM technology. Under electronic microscope, the morphology of A549 cell showed nuclear karyopycnosis, chromatin agglutination and typical apoptotic body when the cell was treated with thaspine. Thaspine has the effects of anti-tumor and inducing apoptosis.

  10. Long non-coding RNAs and mRNAs profiling during spleen development in pig.

    Science.gov (United States)

    Che, Tiandong; Li, Diyan; Jin, Long; Fu, Yuhua; Liu, Yingkai; Liu, Pengliang; Wang, Yixin; Tang, Qianzi; Ma, Jideng; Wang, Xun; Jiang, Anan; Li, Xuewei; Li, Mingzhou

    2018-01-01

    Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and long non-coding RNAs (lncRNAs) expressed during pig spleen development has not been achieved. LncRNAs are known to participate in regulatory networks for an array of biological processes. Here, we constructed 18 RNA libraries from developing fetal pig spleen (55 days before birth), postnatal pig spleens (0, 30, 180 days and 2 years after birth), and the samples from the 2-year-old Wild Boar. A total of 15,040 lncRNA transcripts were identified among these samples. We found that the temporal expression pattern of lncRNAs was more restricted than observed for protein-coding genes. Time-series analysis showed two large modules for protein-coding genes and lncRNAs. The up-regulated module was enriched for genes related to immune and inflammatory function, while the down-regulated module was enriched for cell proliferation processes such as cell division and DNA replication. Co-expression networks indicated the functional relatedness between protein-coding genes and lncRNAs, which were enriched for similar functions over the series of time points examined. We identified numerous differentially expressed protein-coding genes and lncRNAs in all five developmental stages. Notably, ceruloplasmin precursor (CP), a protein-coding gene participating in antioxidant and iron transport processes, was differentially expressed in all stages. This study provides the first catalog of the developing pig spleen, and contributes to a fuller understanding of the molecular mechanisms underpinning mammalian spleen development.

  11. Use of the dog spleen for studying effects of irradiation and chemotherapeutic agents, with suggested uses of other organs

    International Nuclear Information System (INIS)

    Wilcox, L.D.; De Rose, G.; Cooke, D.

    1976-01-01

    The irradiation of the exteriorized spleen of the dog, with the animal lead-shielded, produced constant changes in the white blood cells. The time of recovery from the irradiation effect was determined. The normal canine spleen could handle live pneumococci injected into the splenic artery, as proven by sterile cultures of splenic vein samples. The size of the bolus used was determined by repeated trials and proved to be one billion pneumococci per pound of body weight. The capacity of the irradiated spleen to handle this number of pneumococci was impaired. It was found that whole body irradiation, nitrogen mustard, thio-tepa, cyclophosphamide, methotrexate, 5-fluorouracil, vinblastine, and azothioprine all impaired this capacity of the spleen. The dose of the chemotherapeutic agent was the same in milligrams per kilogram as that used in the cancer clinic. A method for determining the recovery time following the use of one or more agents was developed with the repeated use of the spleen model. By extending the methods used with the spleen it was found that similar use could be made, usually without surgery, of the liver, gut, and lungs

  12. COMPARATIVE GROSS AND HISTOMORPHOLOGICAL STUDIES ON THE SPLEEN OF SHEEP AND GOAT OF JAMMU REGION OF INDIA

    Directory of Open Access Journals (Sweden)

    Shalini Suri

    2017-12-01

    Full Text Available The study was conducted on the histology and micrometry of the spleen of sheep and goat of Jammu region. The spleen of goat was quadrangular whereas that of sheep was triangular. The biometrical measurements of the spleens of sheep and goat revealed that the weight of spleen of sheep was 81.39 ± 12.79 gm while that of goat was 64.48 ± 7.82 gm. The length of the spleen was 12.70 ± 0.81 cm and 11.48 ± 0.73 cm in sheep and goat, respectively. The width of spleen of sheep was recorded to be 9.26 ± 0.38 cm and that of goat was measured as 9.37 ± 0.79 cm and the thickness of spleen was found to be 2.69 ± 0.2 cm and 2.37 ± 0.21 cm in sheep and goat, respectively. Histologically, spleen was covered by thick capsule with thickness 282.27 ± 14.88 µ in goat and 150.13 ± 8.14 µ in sheep. The thickness of trabeculae in goat was 224.67 ± 67 µ and in sheep was 104.35 ± 8.92 µ. Average diameter of white pulp was 478.20 ± 26.88 µ in sheep and 412.22 ± 47.85 µ in goat. Number of white pulps per field at 100 X magnification was 1.30 ± 0.21 in sheep and 1.60 ± 023 in goat. Similarly, number of white pulps per mm2 was 1.32 ± 0.22 in sheep and 1.62 ± 023 in goat. Red pulp consisted of spleenic cords and sinusoids. Sinusoids were lined by endothelial cells with large nuclei bulging into the sinusoidal lumen.

  13. The effect of climbing Mount Everest on spleen contraction and increase in hemoglobin concentration during breath holding and exercise.

    Science.gov (United States)

    Engan, Harald K; Lodin-Sundström, Angelica; Schagatay, Fanny; Schagatay, Erika

    2014-04-01

    Release of stored red blood cells resulting from spleen contraction improves human performance in various hypoxic situations. This study determined spleen volume resulting from two contraction-evoking stimuli: breath holding and exercise before and after altitude acclimatization during a Mount Everest ascent (8848 m). Eight climbers performed the following protocol before and after the climb: 5 min ambient air respiration at 1370 m during rest, 20 min oxygen respiration, 20 min ambient air respiration at 1370 m, three maximal-effort breath holds spaced by 2 min, 10 min ambient air respiration, 5 min of cycling at 100 W, and finally 10 min ambient air respiration. We measured spleen volume by ultrasound and capillary hemoglobin (HB) concentration after each exposure, and heart rate (HR) and arterial oxygen saturation (Sao2) continuously. Mean (SD) baseline spleen volume was unchanged at 213 (101) mL before and 206 (52) mL after the climb. Before the climb, spleen volume was reduced to 184 (83) mL after three breath holds, and after the climb three breath holds resulted in a spleen volume of 132 (26) mL (p=0.032). After exercise, the preclimb spleen volume was 186 (89) mL vs. 112 (389) mL) after the climb (p=0.003). Breath hold duration and cardiovascular responses were unchanged after the climb. We concluded that spleen contraction may be enhanced by altitude acclimatization, probably reflecting both the acclimatization to chronic hypoxic exposure and acute hypoxia during physical work.

  14. The Alpha-Melanocyte Stimulating Hormone Induces Conversion of Effector T Cells into Treg Cells

    Directory of Open Access Journals (Sweden)

    Andrew W. Taylor

    2011-01-01

    Full Text Available The neuropeptide alpha-melanocyte stimulating hormone (α-MSH has an important role in modulating immunity and homeostasis. The production of IFN-γ by effector T cells is suppressed by α-MSH, while TGF-β production is promoted in the same cells. Such α-MSH-treated T cells have immune regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft rejection. Previous characterizations of the α-MSH-induced Treg cells showed that the cells are CD4+ T cells expressing the same levels of CD25 as effector T cells. Therefore, we further analyzed the α-MSH-induced Treg cells for expression of effector and regulatory T-cell markers. Also, we examined the potential for α-MSH-induced Treg cells to be from the effector T-cell population. We found that the α-MSH-induced Treg cells are CD25+  CD4+ T cells that share similar surface markers as effector T cells, except that they express on their surface LAP. Also, the α-MSH treatment augments FoxP3 message in the effector T cells, and α-MSH induction of regulatory activity was limited to the effector CD25+ T-cell population. Therefore, α-MSH converts effector T cells into Treg cells, which suppress immunity targeting specific antigens and tissues.

  15. Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.

    Science.gov (United States)

    Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie

    2017-05-01

    Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.

  16. Heat-induced alterations in the cell nucleus

    International Nuclear Information System (INIS)

    Kampinga, H.H.

    1989-01-01

    Hyperthermia may kill eukaryotic cells and may also enhance the radiosensitivity of those cells that survive the heat treatment. Clinically, the possible use of hyperthermia as an adjuvant in the radiotherapeutic treatment of cancer needs the understanding of mechanisms that underlay heat-induced cell death and radiosensitization. By in vitro heating of established human (HeLaS3) and rodent (Ehrlich Ascites Tumor and LM fibroblast) cell lines, both killing and radiosensitization were investigated. (author). 1067 refs.; 76 figs.; 19 tabs

  17. Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Bishop, Matthew T; Diack, Abigail B; Ritchie, Diane L; Ironside, James W; Will, Robert G; Manson, Jean C

    2013-04-01

    Blood transfusion has been identified as a source of human-to-human transmission of variant Creutzfeldt-Jakob disease. Three cases of variant Creutzfeldt-Jakob disease have been identified following red cell transfusions from donors who subsequently developed variant Creutzfeldt-Jakob disease and an asymptomatic red cell transfusion recipient, who did not die of variant Creutzfeldt-Jakob disease, has been identified with prion protein deposition in the spleen and a lymph node, but not the brain. This individual was heterozygous (MV) at codon 129 of the prion protein gene (PRNP), whereas all previous definite and probable cases of variant Creutzfeldt-Jakob disease have been methionine homozygotes (MM). A critical question for public health is whether the prion protein deposition reported in peripheral tissues from this MV individual correlates with infectivity. Additionally it is important to establish whether the PRNP codon 129 genotype has influenced the transmission characteristics of the infectious agent. Brain and spleen from the MV blood recipient were inoculated into murine strains that have consistently demonstrated transmission of the variant Creutzfeldt-Jakob disease agent. Mice were assessed for clinical and pathological signs of disease and transmission data were compared with other transmission studies in variant Creutzfeldt-Jakob disease, including those on the spleen and brain of the donor to the index case. Transmission of variant Creutzfeldt-Jakob disease was observed from the MV blood recipient spleen, but not from the brain, whereas there was transmission from both spleen and brain tissues from the red blood cell donor. Longer incubation times were observed for the blood donor spleen inoculum compared with the blood donor brain inoculum, suggesting lower titres of infectivity in the spleen. The distribution of vacuolar pathology and abnormal prion protein in infected mice were similar following inoculation with both donor and recipient spleen

  18. Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt–Jakob disease

    Science.gov (United States)

    Bishop, Matthew T.; Diack, Abigail B.; Ritchie, Diane L.; Ironside, James W.; Will, Robert G.

    2013-01-01

    Blood transfusion has been identified as a source of human-to-human transmission of variant Creutzfeldt–Jakob disease. Three cases of variant Creutzfeldt–Jakob disease have been identified following red cell transfusions from donors who subsequently developed variant Creutzfeldt–Jakob disease and an asymptomatic red cell transfusion recipient, who did not die of variant Creutzfeldt–Jakob disease, has been identified with prion protein deposition in the spleen and a lymph node, but not the brain. This individual was heterozygous (MV) at codon 129 of the prion protein gene (PRNP), whereas all previous definite and probable cases of variant Creutzfeldt–Jakob disease have been methionine homozygotes (MM). A critical question for public health is whether the prion protein deposition reported in peripheral tissues from this MV individual correlates with infectivity. Additionally it is important to establish whether the PRNP codon 129 genotype has influenced the transmission characteristics of the infectious agent. Brain and spleen from the MV blood recipient were inoculated into murine strains that have consistently demonstrated transmission of the variant Creutzfeldt–Jakob disease agent. Mice were assessed for clinical and pathological signs of disease and transmission data were compared with other transmission studies in variant Creutzfeldt–Jakob disease, including those on the spleen and brain of the donor to the index case. Transmission of variant Creutzfeldt–Jakob disease was observed from the MV blood recipient spleen, but not from the brain, whereas there was transmission from both spleen and brain tissues from the red blood cell donor. Longer incubation times were observed for the blood donor spleen inoculum compared with the blood donor brain inoculum, suggesting lower titres of infectivity in the spleen. The distribution of vacuolar pathology and abnormal prion protein in infected mice were similar following inoculation with both donor and

  19. Method of monolayer cultures of the guinea pig spleen used to evaluate the radioprotective action of mexamine on the survival of colony-forming cells. [Method of monolayer cultures, quantitative estimation of radioprotective action of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Baisogolov, G D; Rudakova, S F; Rudakov, I A; Konoplyannikov, A G [Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii

    1976-01-01

    Dose dependent survival of colony-forming splenic cells of guinea pigs has been studied after ..gamma..-irradiation in vitro. The average lethal dose (D/sub 0/) for colony-forming cells is 245 rads, the extrapolation number - 1.5. Radiosensitivity of the splenic cells is markedly lower than that of the bone marrow cells (128 rads). After intraperitoneal administration of mexamine (150 mg/kg) to guinea pigs 10-15 min before irradiation, D/sub 0/ increases up to 319 rads, extrapolation number is 1.4, and DRF is 1.3.

  20. Low dose radiation induced protein and its experimental and ophthalmic clinical research

    International Nuclear Information System (INIS)

    Shen Wei; Su Liaoyuan; Liu Fenju; Ding Jie; Li Longbiao; Pan Chengsi

    2001-01-01

    The protective effects of low dose radiation (LDR) induced protein on cellular impairments caused by some harmful chemical and physical factors were studied. Male Kunming mice were irradiated with LDR, then the spleen cells of the mice were broken with ultrasonic energy and then ultracentrifugalized. The supernatant solution contained with LDR induced protein. The newly emerging protein was detected by gel filtration and its molecular weight was determined by gel electrophoresis. The content of newly emerging protein (LDR induced protein) was determined by Lowry's method. The method of isotope incorporation was used to observe the biological activity and its influence factors, the protective effects of LDR induced protein on the cells impaired by irradiating with ultraviolet (UV), high doses of 60 Co γ-rays and exposed to heat respectively, and the stimulative effects of LDR induced protein on human peripheral blood lymphocytes. Newly emerging protein has been observed in the experiment. The molecular weight of the protein is in the region 76.9 KD+- - 110.0 KD+-, the yield of the protein was 613.33 +- 213.42 μg per 3 x 10 7 spleen cells. DPM values (isotope were incorporated) of normal and injured mice spleen cells increased significantly after stimulating with the solution contained LDR induced protein. It is concluded that LDR induced protein could be obtained from mice spleen cells exposed to 5 - 15 cGy radiation for 2 - 16 h. The protein had biological activity and was able to stimulate the transformation of the spleen cells in vitro. It had obvious protective effects on some impaired cells caused by high dose radiation, UV radiation, heat and so on. It also had stimulative effects on the transformation of peripheral blood T and B lymphocytes of healthy individual and patients with eye diseases. It indicates that LDR induced protein increased immune function of human

  1. Casticin impairs cell growth and induces cell apoptosis via cell cycle arrest in human oral cancer SCC-4 cells.

    Science.gov (United States)

    Chou, Guan-Ling; Peng, Shu-Fen; Liao, Ching-Lung; Ho, Heng-Chien; Lu, Kung-Wen; Lien, Jin-Cherng; Fan, Ming-Jen; La, Kuang-Chi; Chung, Jing-Gung

    2018-02-01

    Casticin, a polymethoxyflavone, present in natural plants, has been shown to have biological activities including anti-cancer activities. Herein, we investigated the anti-oral cancer activity of casticin on SCC-4 cells in vitro. Viable cells, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS) production, and Ca 2+ production, levels of ΔΨ m and caspase activity were measured by flow cytometric assay. Cell apoptosis associated protein expressions were examined by Western blotting and confocal laser microscopy. Results indicated that casticin induced cell morphological changes, DNA condensation and damage, decreased the total viable cells, induced G 2 /M phase arrest in SCC-4 cells. Casticin promoted ROS and Ca 2+ productions, decreases the levels of ΔΨ m , promoted caspase-3, -8, and -9 activities in SCC-4 cells. Western blotting assay demonstrated that casticin affect protein level associated with G2/M phase arrest and apoptosis. Confocal laser microscopy also confirmed that casticin increased the translocation of AIF and cytochrome c in SCC-4 cells. In conclusion, casticin decreased cell number through G 2 /M phase arrest and the induction of cell apoptosis through caspase- and mitochondria-dependent pathways in SCC-4 cells. © 2017 Wiley Periodicals, Inc.

  2. MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Debin Ma

    2015-09-01

    Full Text Available MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy.

  3. Ionizing radiation induces apoptosis in hematopoietic stem and progenitor cells

    International Nuclear Information System (INIS)

    Meng, A.; Zhou, D.; Geiger, H.; Zant, G.V.

    2003-01-01

    The aims of this study was to determine if ionizing radiation (IR) induces apoptosis in hematopoietic stem (HSC) and progenitor cells. Lin-cells were isolated from mouse bone marrow (BM) and pretreated with vehicle or 100 μM z-VAD 1 h prior to exposure to 4 Gy IR. The apoptotic and/or necrotic responses of these cells to IR were analyzed by measuring the annexin V and/or 7-AAD staining in HSC and progenitor populations using flow cytometry, and hematopoietic function of these cells was determined by CAFC assay. Exposure of Lin-cells to IR selectively decreased the numbers of HSC and progenitors in association with an increase in apoptosis in a time-dependent manner. Pretreatment of Lin- cells with z-VAD significantly inhibited IR-induced apoptosis and the decrease in the numbers of HSC and progenitors. However, IR alone or in combination with z-VAD did not lead to a significant increase in necrotic cell death in either HSC or progenitors. In addition, pretreatment of BM cells with z-VAD significantly attenuated IR-induced reduction in the frequencies of day-7, -28 and -35 CAFC. Exposure of HSC and progenitors to IR induces apoptosis. The induction of HSC and progenitor apoptosis contributes to IR-induced suppression of their hematopoietic function

  4. Capecitabine treatment of HCT-15 colon cancer cells induces ...

    African Journals Online (AJOL)

    HCT-15 cells caused condensation of DNA and induced apoptosis in a concentration- ... Conclusion: Capecitabine treatment causes inhibition of colon cancer growth via the mitochondrial ... fluoropyrimidine aimed to selectively transfer 5-.

  5. Aspartame-induced apoptosis in PC12 cells.

    Science.gov (United States)

    Horio, Yukari; Sun, Yongkun; Liu, Chuang; Saito, Takeshi; Kurasaki, Masaaki

    2014-01-01

    Aspartame is an artificial sweetner added to many low-calorie foods. The safety of aspartame remains controversial even though there are many studies on its risks. In this study, to understand the physiological effects of trace amounts of artificial sweetners on cells, the effects of aspartame on apoptosis were investigated using a PC12 cell system. In addition, the mechanism of apoptosis induced by aspartame in PC12 cells and effects on apoptotic factors such as cytochrome c, apoptosis-inducing factor, and caspase family proteins were studied by Western blotting and RT-PCR. Aspartame-induced apoptosis in PC12 cells in a dose-dependent manner. In addition, aspartame exposure increased the expressions of caspases 8 and 9, and cytochrome c. These results indicate that aspartame induces apoptosis mainly via mitochondrial pathway involved in apoptosis due to oxigen toxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Suppression of T cell-induced osteoclast formation

    Energy Technology Data Exchange (ETDEWEB)

    Karieb, Sahar; Fox, Simon W., E-mail: Simon.fox@plymouth.ac.uk

    2013-07-12

    Highlights: •Genistein and coumestrol prevent activated T cell induced osteoclast formation. •Anti-TNF neutralising antibodies prevent the pro-osteoclastic effect of activated T cells. •Phytoestrogens inhibit T cell derived TNF alpha and inflammatory cytokine production. •Phytoestrogens have a broader range of anti-osteoclastic actions than other anti-resorptives. -- Abstract: Inhibition of T cell derived cytokine production could help suppress osteoclast differentiation in inflammatory skeletal disorders. Bisphosphonates are typically prescribed to prevent inflammatory bone loss but are not tolerated by all patients and are associated with an increased risk of osteonecrosis of the jaw. In light of this other anti-resorptives such as phytoestrogens are being considered. However the effect of phytoestrogens on T cell-induced osteoclast formation is unclear. The effect of genistein and coumestrol on activated T cell-induced osteoclastogenesis and cytokine production was therefore examined. Concentrations of genistein and coumestrol (10{sup −7} M) previously shown to directly inhibit osteoclast formation also suppressed the formation of TRAP positive osteoclast induced by con A activated T cells, which was dependent on inhibition of T cell derived TNF-α. While both reduced osteoclast formation their mechanism of action differed. The anti-osteoclastic effect of coumestrol was associated with a dual effect on con A induced T cell proliferation and activation; 10{sup −7} M coumestrol significantly reducing T cell number (0.36) and TNF-α (0.47), IL-1β (0.23) and IL-6 (0.35) expression, whereas genistein (10{sup −7} M) had no effect on T cell number but a more pronounced effect on T cell differentiation reducing expression of TNF-α (0.49), IL-1β (0.52), IL-6 (0.71) and RANKL (0.71). Phytoestrogens therefore prevent the pro-osteoclastic action of T cells suggesting they may have a role in the control of inflammatory bone loss.

  7. Comparative erythrocyte deformability investig