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1.
《Immunopharmacology and immunotoxicology》2013,35(1-2):21-38
AbstractIn a preceeding paper we characterized the in vivo and in vitro induction of cytotoxic effector cells elicited by a novel synthetic immuno-stimulator 7-thia-8-oxoguanosine (7T80G)2. In the present study we further characterized the cells responsible for the induced cytotoxicity and the mechanisms together with the lymphokines mediating the immunological response to 7T80G. Removal of macrophages from 7T80G activated spleen cell suspensions by various methods resulted in a significant increase in cytotoxicity to YAC-1 targets. 7T80G induced effectors did not exert cytotoxic effect on macrophage sensitive P815 target cells. In vivo activated effectors when incubated with anti-asialo-GM1 antibody plus complement lost completely their ability to lyse YAC-1 targets. Together, these findings indicate that the 7T80G induced effector cells are not macrophage like. Spleen cells from nude mice were readily activated by 7T80G. The induced effectors were resistant to complement mediated lysis using anti-L3T4, anti-Lyt1 or anti-Lyt2 antibodies. Pretreatment of spleen cells with macrophage depleting agents both, in vitro and in vivo and subsequent activation of cells by 7T80G resulted in effectors with reduced cytotoxicity.When injected in vivo, 7T80G induced strong IFN production which paralelled the kinetics of NK cell activation. Furthermore, antibodies to α&β-IFN but not to γ-IFN diminished the induction of the cytotoxic activity. Although these findings suggest that activation of NK cells by 7T80G is most likely to be mediated by α&β-IFN involvement of other cytokines can not be ruled out. 相似文献
2.
We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T8OG)2 inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3). Since certain tumor metastases and virus infected cells are targets to natural killer cells (NK cells), we now investigated whether 7T8OG is capable of activating NK cells in mice using NK cell sensitive YAC-1 and B16 and NK cell insensitive P815 targets. CBA/CaJ spleen cells incubated in vitro with 7T8OG at concentrations ranging from 0.005 to 0.5 mM responded with increased NK cell activity (32-62%) compared to controls (4-8%) to YAC-1 targets. Similar levels of augmentation in NK cell activity were observed when 40-168 mg/kg of 7T8OG was administered in vivo. In addition to the spleen, 7T8OG activated NK cells in the bone marrow (BM), the lungs, the liver, and in peritoneal exudate cells (PE). Although 7T8OG elicited activation of NK cells was observed as early as three hours after treatment, the maximal activity was observed after 24 h in the spleen; 12 h in the BM; 48 h in the lungs, and 72 h in PE. Administration of the drug by s.c., i.v., and i.p. routes all induced activation of NK cells in spleen, BM and PE. 7T8OG was found to activate NK cells in seven inbred and an outbred mouse strain, suggesting that the induced cytotoxicity against allogeneic and syngeneic tumor cells is not strain specific as well as independent of MHC restriction. C3H/He, CBA/CaJ and BDF/1 displayed higher levels of increased NK cell activity, whereas AKR mice were low responders. Low concentrations of IL-2 (0.25-5 U/ml) that induce little or no NK cell activity, when used in combination with 7T8OG, elicited significant enhancement of NK cell cytotoxicity. In contrast, IFN and 7T8OG showed no such synergism. 相似文献
3.
M Coli? S Gasi? S Vasiliji? V Pejanovi? D Jandri? L Medi?-Mijacevi? L Raki? 《Immunology letters》1999,69(3):293-300
7-thia-8-oxoguanosine (immunosine) is a nucleoside analogue with immunoenhancing activity. In this work, its effects on proliferation of thymocytes in vitro were studied. It was found that immunosine stimulated proliferation of thymocytes both of mice and rats. The stimulatory effect depended on antigen presenting cells (APC), since thymocytes depleted of accessory cells did not proliferate to immunosine. In addition, pretreatment of APC with immunosine for 24 h significantly increased proliferation of thymocytes. Immunosine stimulated interleukin 2 (IL-2) production and the expression of activation markers (CD25 and CD71). The upregulation of CD25 (alpha subunit of IL-2R) was detected both on thymocytes and thymic dendritic cells. Proliferation of thymocytes in the presence of immunosine was predominantly mediated by IL-2 since blocking IL-2Ralpha by specific monoclonal antibodies inhibited cell proliferation by 65-85%. 相似文献
4.
B S Sharma S Mhaskar L Balazs A Jin D F Smee 《Immunopharmacology and immunotoxicology》1992,14(1-2):21-38
In a preceding paper we characterized the in vivo and in vitro induction of cytotoxic effector cells elicited by a novel synthetic immuno-stimulator 7-thia-8-oxoguanosine (7T8OG)2. In the present study we further characterized the cells responsible for the induced cytotoxicity and the mechanisms together with the lymphokines mediating the immunological response to 7T8OG. Removal of macrophages from 7T8OG activated spleen cell suspensions by various methods resulted in a significant increase in cytotoxicity to YAC-1 targets. 7T8OG induced effectors did not exert cytotoxic effect on macrophage sensitive P815 target cells. In vivo activated effectors when incubated with anti-asialo-GM1 antibody plus complement lost completely their ability to lyse YAC-1 targets. Together, these findings indicate that the 7T8OG induced effector cells are not macrophage like. Spleen cells from nude mice were readily activated by 7T8OG. The induced effectors were resistant to complement mediated lysis using anti-L3T4, anti-Lyt1 or anti-Lyt2 antibodies. Pretreatment of spleen cells with macrophage depleting agents both, in vitro and in vivo and subsequent activation of cells by 7T8OG resulted in effectors with reduced cytotoxicity. When injected in vivo, 7T8OG induced strong IFN production which paralelled the kinetics of NK cell activation. Furthermore, antibodies to alpha & beta-IFN but not to gamma-IFN diminished the induction of the cytotoxic activity. Although these findings suggest that activation of NK cells by 7T8OG is most likely to be mediated by alpha & beta-IFN involvement of other cytokines can not be ruled out. 相似文献
5.
Colić M Gasić S Vucević D Pavicić L Popović P Jandrić D Medić-Mijacević L Rakić L 《International journal of immunopharmacology》2000,22(3):203-212
7-thia-8-oxoguanosine (immunosine) is a guanosine analogue showing immunostimulatory activity on different components of the immune system, including B lymphocytes, natural killer cells and macrophages. However, little is known about its effect on T-cell functions. In this work it was demonstrated that immunosine at concentrations between 10 microM and 1 mM stimulated proliferation of rat thymocytes in vitro triggered by suboptimal concentrations of concanavalin A (Con A). The effect correlated with increased interleukin 2 (IL-2) production, upregulation of the IL-2 receptor alpha (IL-2Ralpha) expression and decreased apoptosis of thymocytes in comparison to the effect of Con A alone. 相似文献
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7.
Zahran Asmaa M. Abdel-Rahim Mona H. Elsayh Khalid I. Hassanien Manal M. Mahran Safaa A. Hetta Helal F. 《Archivum immunologiae et therapiae experimentalis》2019,67(3):161-169
Archivum Immunologiae et Therapiae Experimentalis - The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus erythematosus (SLE) is... 相似文献
8.
Treatment of Swiss albino mice with histamine enhanced the clearance of natural killer (NK)-cell sensitive YAC-1 lymphoma and B16/F10 melanoma cells from lung tissue in vivo , but did not affect the elimination of NK-cell-insensitive P815mastocytoma cells. The effect of histamine was apparently mediated by H2 -type histamine receptors (H2 R) since it was blocked by ranitidine, an H2 R antagonist. Histamine did not affect clearance of tumour cells in animalsdepleted of NK cells in vivo by treatment with antibodies to asialo-GM1 or NK1.1. The effect of histamine was time-dependent: pretreatment with histamine for 3 h significantly augmented the clearance of YAC-1 cells, whereas, pretreatmentwith histamine for 5 min was ineffective. Histamine potentiated the anti-tumour properties of NK-cell activators such as interleukin-2 (IL-2) or interferon-α (IFN-α) in vivo . None of these lymphokines significantly affected theclearance of YAC-1 cells unless animals were concomitantly treated with histamine. Treatment with ranitidine alone reduced the in vivo clearance of YAC-1 cells from lungs but did not affect the clearance of NK-cell-insensitive P815 cells. Effects of ranitidine on NK-cell function in vivo were not shared by a chemical control to ranitidine, AH20239AA, thus indicating that the inhibition of NK-cells results from H2 R antagonism rather than non-specific toxicity. It is concludedthat histaminergic mechanisms may be involved in the regulation of NK cell function in vivo 相似文献
9.
《International reviews of immunology》2013,32(3-4):415-437
NIC cells have the ability to destroy tumor cells by two main cytotoxic pathways, the well-known perforin/granzyme-mediated secretory/necrotic killing and the newly defined TNF family ligand-mediated apoptotic killing. The former mechanism is operative mainly against a few cultured leukemia cell targets, while the latter mediates substantial activity against most tumor cell targets. It also appears from emerging data that the apoptotic mechanism is the main antitumor pathway in vivo. This review is focused on the apoptotic mechanism of killing, the molecules and cell signaling pathways involved in this process, and its potential biologic significance along with its relation to the secretory/necrotic cytolytic pathway. 相似文献
10.
粗江蓠多糖对辐射损伤小鼠NK细胞的影响 总被引:1,自引:0,他引:1
目的:研究粗江蓠多糖(Gracilaria Gigas Harvey Polysaccharides,GHPS)对辐射损伤小鼠NK细胞的影响。方法:采用60Coγ射线5Gy全身照射小鼠制造辐射损伤模型,通过乳酸脱氢酶释放法检测不同剂量(10mg/kg,20mg/kg,40mg/kg)的GHPS对辐射损伤小鼠NK细胞杀伤靶细胞能力的影响。结果:辐射对照组小鼠接受60Coγ射线5Gy照射后,NK细胞的活性显著低于正常对照组(P〈0.01)。经腹腔注射(10、20、40)mg/kg GHPS,再接受γ射线5Gy照射后,小鼠NK细胞活性明显高于辐射对照组(P〈0.01),并有剂量依赖性。结论:5Gyγ射线可以抑制小鼠NK细胞杀伤靶细胞的活性,而GHPS对辐射损伤小鼠的NK细胞有保护作用。 相似文献
11.
C. CANTONI A. CAMBIAGGI S. SFORZINI A. POGGI M. VIALE R. BIASSONI S. FERRINI 《Scandinavian journal of immunology》1994,39(4):373-379
Previously, the authors have described a molecule, identified by the LD6 monoclonal antibody (MoAb), present at the cell surface of long-term cultured T and Natural Killer (NK) cells which is involved in cell triggering. In the study described here the authors used biotin surface labelling and immunoprecipitation to show that LD6 MoAb recognizes a surface protein of approximately 65 kDa. In combination with submitogenic concentrations ofphorbol esters (PMA), LD6 MoAb was able to induce accumulation of mRNA specific for GM-CSF, γ-IFN and TNF-α and release of these cytokines by LD6+ T-cell lines. Both lymphokine production and lymphokine-specific mRNA accumulation induced by the LD6 MoAb were blocked totally by Cyclosporin A (CsA). To investigate the mechanism(s) of signal transduction through this activatory pathway, the authors performed Ca++ mobilization experiments. The results of these experiments suggested a role for Ca++ in signal transduction. The Ca++ mobilization induced by LD6 MoAb cross-linking could be inhibited totally by the use of pertus.sis toxin, indicating a possible role for G proteins in signalling through the LD6 MoAb-reactive molecule. Western blot analysis performed with an anti-phosphotyrosine antibody did not suggest that tyrosine kinase activation has a role. 相似文献
12.
应激对小鼠T、B细胞分裂原反应性及天然杀伤细胞活性的影响 总被引:1,自引:0,他引:1
自Jerne提出免疫网络学说,对免疫调节的研究日益深入。但这些工作多限于研究免疫系统内部的相互作用,而忽略了免疫系统外的因素对免疫应答的影响。近年来有些作者注意到神经-内分泌系统对免疫反应的调控作用,应激的研究应为其中之一。应激往往引起神经-内分泌系统的一系列变化,并导致免疫功能的改变。手术、创伤、疼痛引起的应激反应,往往造成患者的抗感染、抗肿瘤的能力下降,认为与应激介导的免疫抑制效应有关。但未见有关手术应激的动物实验报告。本文重点研究了手术应激动物模型的建立,证明此种应激可明显抑制小鼠的分裂原反应性及NK活性。比较不同分裂原反应性受抑的动力变化,发现不同分裂原反应性对手术应激的抑制效应的敏感性不 相似文献
13.
In-Cheul Jeung Youn-Jee Chung Boah Chae So-Yeon Kang Jae-Yen Song Hyun-Hee Jo Young-Ok Lew Jang-Heub Kim Mee-Ran Kim 《International journal of medical sciences》2015,12(1):42-47
Background and Aim: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosisMaterials and Methods: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker.Results: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p = 0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p = 0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p = 0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p = 0.014) in stage III/IV.Conclusions: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results open new role of helixor A as an imune modulation therapy, or in combination with hormonal agents, for the treatment of endometriosis. 相似文献
14.
Activation of Natural Killer Cells in Arthritis-Susceptible but Not Arthritis-Resistant Mouse Strains following Borrelia burgdorferi Infection 下载免费PDF全文
Infection of susceptible mouse strains with Borrelia burgdorferi, the agent of Lyme disease, results in the development of arthritis. Components of the innate immune system may be important mediators of this pathology. To investigate the potential role of NK cells in development of experimental Lyme arthritis, we examined their activation in vivo in both resistant and susceptible mouse strains. Following inoculation of B. burgdorferi into the footpad, lymph node NK cells from susceptible C3H/HeJ (C3H) mice produced more gamma interferon than NK cells from resistant DBA/2J mice. Lymph node cells from susceptible C3H and AKR mice also had increased ability to lyse YAC-1 target cells 2 days following infection. Antibody depletion of NK cells from susceptible mice, however, did not alter the development of arthritis following B. burgdorferi challenge. In addition, NK cell depletion had little effect on spirochete burden. Thus, there is a marked activation of NK cells in susceptible mouse strains following infection. Although NK cells are not absolutely required for arthritis, events occurring prior to NK cell activation might be important in mediating pathology in experimental Lyme disease. 相似文献
15.
Augmentation of Natural Killer Cell Activity by Anti-Host Delayed-Type Hypersensitivity during the Graft-versus-Host Reaction in Mice 总被引:2,自引:0,他引:2
During a graft-versus-host (GVH) reaction in unirradiated F1 hybrid mice there is a generalized activation of natural killer (NK) cells. We have examined whether the enhanced NK activity is due to an F1 resistance mechanism directed at the parental cells used to induce the GVH reaction. Spleen cells of C57BL/10 origin induce much more NK cell activation in B10F1 hybrids than the opposite parental type, despite a similar intensity of systemic GVH reactions. However, this does not correlate with in vivo resistance of mice with GVH reaction to a local challenge dose of B10 cells. NK cell activation in (CBA X BALB/c)F1 mice with GVH reaction involves both host and donor cells and is preceded by an anti-host delayed-type hypersensitivity (DTH) response. B10 cells have a greater ability to induce DTH in B10F1 mice than cells from the opposite parent. We propose that NK cells are one group of non-specific effector cells recruited by DTH in a GVH reaction and may contribute to the tissue pathology. 相似文献
16.
S. E. McNerlan I. M. Rea H. D. Alexander T. C. M. Morris 《Journal of clinical immunology》1998,18(1):31-38
Aging has been shown to be accompanied by various changes in the lymphocyte subset distribution in the elderly. We have investigated more fully, and in a large number of subjects, age-related changes within several subpopulations bearing natural killer (NK) cell-associated surface antigens and changes in several cytokines involved in NK cell expansion. A total of 229 healthy subjects from all decades of life from 20 to 98 years of age was included in this cross-sectional study. A significant increase with age was found in both the absolute counts and the proportions of CD3–CD(16+56)+, CD3+CD(16+56)+, CD57+CD8+, CD57+CD8(low)+, and CD57+CD8– cells, whereas the CD57+CD8(high)+ subset, which may represent the cytolytic T cell population more precisely, showed less change with age. Some evidence is also provided to suggest that these expanded NK cell populations are in an activated state. Soluble IL-2 receptor levels were also found to increase significantly with age and correlated with certain NK cell subsets. Although the functions of some of these subsets remain to be elucidated, their expansion in the elderly may represent a remodeling of the immune system with increasing age, with an increase in non-MHC-restricted cells perhaps compensating for the previously reported decline in T and B cells in the elderly. Alternatively, increased numbers of these cells may be a direct result of cytokine dysregulation or increased antigenic or neoplastic cell challenge. 相似文献
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18.
《Immunopharmacology and immunotoxicology》2013,35(4):481-497
AbstractThis study investigated whether in vitro immunotherapy with rIL-2 which augments human natural cytotoxicity and generation of lymphokine-activated killer cells diminished or inhibits the severity of therapeutically induced human in vitro NK immunosuppression. We demonstrate that rIL-2 induces a rapid and potent enhancement of cytolytic killing and that pretreatment of effecter cells for one hour with rIL-2 yields effecter cells which are more resistant to drug-induced immunosuppression. Additionally, we demonstrate cells pretreated for 24 hours with rIL-2 were less sensitive to drug inhibitory effects than rIL-2 non-treated or one hour pretreated effecter cells. Our data suggest prophylactic treatment with IL-2 for drug induced immunosuppression is feasible. 相似文献
19.
This study investigated whether in vitro immunotherapy with rIL-2 which augments human natural cytotoxicity and generation of lymphokine-activated killer cells diminished or inhibits the severity of therapeutically induced human in vitro NK immunosuppression. We demonstrate that rIL-2 induces a rapid and potent enhancement of cytolytic killing and that pretreatment of effecter cells for one hour with rIL-2 yields effecter cells which are more resistant to drug-induced immunosuppression. Additionally, we demonstrate cells pretreated for 24 hours with rIL-2 were less sensitive to drug inhibitory effects than rIL-2 non-treated or one hour pretreated effecter cells. Our data suggest prophylactic treatment with IL-2 for drug induced immunosuppression is feasible. 相似文献