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

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     

The Role of Calmodulin in Human Natural Killer Cell Activity

Calcium is known to play an essential role in the lytic mechanism of natural killer cells (NK), which form a subset of large granular lymphocytes. Many of the intracellular effects of calcium are mediated through the calcium-binding protein calmodulin. In this study we have demonstrated that the specific calmodulin inhibitors (naphthalene-sulphonamides) inhibit NK activity in humans at IC50's of 6.9 microM for W7 and 5.2 microM for W13. Comparison of the potency of these compounds with their less active counterparts suggests that NK activity is calmodulin-dependent.     

Stress Causes Reduced Natural Killer Activity in Mice

The natural killer (NK) activity of spleen cells from C57B1/10 mice subjected to standardized stress conditions was reduced when compared with that of untreated controls. Both the total number of nucleated spleen cells and their cytotoxic activity against an NK-sensitive target were reduced. The reduction appeared after induction of stress, and the NK activity was reduced throughout an 8-day stress period.     

Depressed Natural Killer Cell Activity in Schizophrenic Patients

Factors that suppress natural killer (NK) cell activity were examined in a random sample of 73 schizophrenic patients. NK activity in these patients were compared with 25 healthy age, sex and race matched controls. The mean percent of NK activity was 21% in the schizophrenic group compared with 30% percent in the controls. The difference between these two groups was statistically significant. The mean percent of NK activity in the chronic undifferentiated schizophrenic subgroup and schizoaffective subgroup were 20% and 22% respectively. The degree of suppression of NK activity in the chronic undifferentiated subgroup was higher than in the schizoaffective one, but the difference was not statistically significant. The two subgroups were comparable regarding other immune related variables such as total white cell count, neutrophils, lymphocytes, total protein, albumin, globulin, immunoglobulins and stress. The lower impairment of NK activity in the schizoaffective subgroup may be due to their exposure to lithium which can enhance immune functions. Factors associated with significant suppression of NK activity in schizophrenic patients were physical restraint, number of psychotropic medications, number of chronic non-psychiatric diagnoses and race. Psychosocial stressors were associated with suppression of NK activity but it was not statistically significant. Our results identify factors associated with reduced NK activity observed in certain schizophrenic patients and NK activity in these patients may be the result of interaction between various factors.     

Depressed Natural Killer Cell Activity in Schizophrenic Patients

Factors that suppress natural killer (NK) cell activity were examined in a random sample of 73 schizophrenic patients. NK activity in these patients were compared with 25 healthy age, sex and race matched controls. The mean percent of NK activity was 21% in the schizophrenic group compared with 30% percent in the controls. The difference between these two groups was statistically significant. The mean percent of NK activity in the chronic undifferentiated schizophrenic subgroup and schizoaffective subgroup were 20% and 22% respectively. The degree of suppression of NK activity in the chronic undifferentiated subgroup was higher than in the schizoaffective one, but the difference was not statistically significant. The two subgroups were comparable regarding other immune related variables such as total white cell count, neutrophils, lymphocytes, total protein, albumin, globulin, immunoglobulins and stress. The lower impairment of NK activity in the schizoaffective subgroup may be due to their exposure to lithium which can enhance immune functions. Factors associated with significant suppression of NK activity in schizophrenic patients were physical restraint, number of psychotropic medications, number of chronic non-psychiatric diagnoses and race. Psychosocial stressors were associated with suppression of NK activity but it was not statistically significant. Our results identify factors associated with reduced NK activity observed in certain schizophrenic patients and NK activity in these patients may be the result of interaction between various factors.     

Effects of Chloroquine, Mefloquine and Quinine on Natural Killer Cell Activity in vitro

Natural killer (NK) cell activity against K 562 target cells was inhibited by pharmacological concentrations of chloroquine, mefloquine and quinine. The most potent were mefloquine and quinine. The drug-induced inhibition of the NK cell activity was abolished by addition of alpha-interferon (IF) or interleukin 2 (Il-2); preincubation of mononuclear cells with IF or Il-2 followed by addition of anti-malarial drugs decreased the inhibitory effects of the drugs. The drug-induced inhibition of the NK cell activity was not dependent on the presence of monocytes. Using monocyte depleted Percoll fractionated NK cell enriched populations in a single cell agarose assay, it was shown that the inhibitory effects of mefloquine, but not of chloroquine and quinine were due to an inhibition of the formation of effector/target cell conjugates.     

Effects of Serum from Pregnant Versus Nonpregnant Women on Natural Killer Cell Activity

PROBLEM: To test the effect of serum obtained from in vitro fertilization-embryo transfer (IVF-ET) patients on the healthy volunteers natural killer (NK) cell activity. METHOD OF STUDY: Retrospective non-randomized clinical study. Suppressive effect on NK cell activity was measured with serum obtained from 25 pregnant and 24 non-pregnant women during IVF-ET procedure. RESULTS: Suppressive serum effect of volunteers' NK cell activity was significantly higher in pregnant than in non-pregnant women (P < 0.01). CONCLUSIONS: The suppressive activity of serum from pregnant women on NK cell suppression activity was useful in predicting the establishment of a successful pregnancy.     

Natural Killer Cell Activity Test Helps to Suspect Aggressive Natural Killer Cell Leukemia - Diagnostic Challenge

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an aggressive clinical course. We aimed to assess the clinicopathological characteristics of the difficult to diagnose ANKL. During ten years, nine patients with ANKL were diagnosed. All the patients exhibited aggressive clinical course and underwent the BM study to rule out lymphoma and hemophagocytic lymphohistiocytosis (HLH). BM examination showed varying degrees of infiltration of neoplastic cells, which were mainly positive for CD2, CD56, cytoplasmic CD3 and EBV in situ hybridization. Five BM aspirates showed histiocytic proliferation with active heomphagocytosis. Normal or increased NK cell activity test results were obtained from 3 patients who were available for testing. Four had multiple BM studies until diagnosis. An aggressive clinical course and positive EBV in situ hybridization, often with associated secondary HLH, should raise the suspicion of an ANKL. Conducting additional supplementary tests such as NK cell activity and NK cell proportion would be helpful for the diagnosis of ANKL.     

Selective Inhibitory Effects of Stress Hormones on Natural Killer (NK) Cell Activity of Lymphocytes from AIDS Patients

To examine the potential role of stress hormones in the progression of HIV infections, we developed an in vitro model system that investigates the effects of cortisol, adreno-corticotropin-releasing hormone (ACTH) and β-endorphin on the natural killer cell activity of lymphocytes from normal subjects and AIDS patients. The system employs a 4 hr⁵¹Cr release assay and K562 target cells. Direct addition of cortisol (0.05, 0.1, and 0.2 μg/ml) or ACTH (10^-6 to 10^-8 M) to the mixture of effector and prelabeled target cells did not produce any significant immunoregulatory effects on the NK cell activity of normal lymphocytes. Direct addition of β-endorphin (10^-13 to 10^-17 M) to the mixture of effector and prelabeled target cells did not produce any significant immunoregulatory effects on the NK cell activity of lymphocytes from normal or AIDS subjects. However, cortisol and ACTH significantly inhibited the NK activity of lymphocytes from AIDS patients. The selective inhibitory effects of cortisol and ACTH in patients with HIV infections are consistent with a model which proposes that stress related neurohormones and/or neuropeptides may be involved in the progression of HIV infections.     

Effect of Helixor A on Natural Killer Cell Activity in Endometriosis

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.     

In Vitro Effects of Various Metals on Natural Killer Cell Activity in Cultured Human Lymphocytes

Abstract

Heavy metals have been shown to have a differential effects on various aspects of immune response. Recently natural killer cells have been widely investigated due to their purported role in immune surveillance. To ascertain the immunotoxic effects of lead, cadmium, nickel and chromium on natural killer (NK) cell activity in vitro, peripheral blood lymphocytes from normal donors were examined in the presence of different concentrations (10^?5-10^?8 M) of four selected metal salts (cadmium sulphate, lead nitrate, chromium nitrate and nickel sulphate). NK cell activity was evaluated in a 4-h chromium release assay against K562 target cells. All of the metal salts were found to exert no effect on NK cell function in the human concentration range.     

In Vitro Effects of Various Metals on Natural Killer Cell Activity in Cultured Human Lymphocytes

Heavy metals have been shown to have a differential effects on various aspects of immune response. Recently natural killer cells have been widely investigated due to their purported role in immune surveillance. To ascertain the immunotoxic effects of lead, cadmium, nickel and chromium on natural killer (NK) cell activity in vitro, peripheral blood lymphocytes from normal donors were examined in the presence of different concentrations (10^-5-10^-8 M) of four selected metal salts (cadmium sulphate, lead nitrate, chromium nitrate and nickel sulphate). NK cell activity was evaluated in a 4-h chromium release assay against K562 target cells. All of the metal salts were found to exert no effect on NK cell function in the human concentration range.     

Inhibition of Natural Killer Cell Activity by Antigen-Antibody Complexes

The natural killer (NK) cell activity of human peripheral blood mononuclear cells was found to be inhibited by precipitated tetanus toxoid anti-tetanus toxoid complexes (Te/aTe) as well as soluble Te/aTe. Preincubation of the immune complexes with protein A decreased the inhibition of NK cell activity. When mononuclear cells were preincubated with interferon (IF) or interleukin 2 (Il-2) before incubation with Te/aTe, the immune complex-induced inhibition was decreased, while IF or Il-2 added after incubation with the immune complexes had no effect. Using NK cell-enriched suspensions in a single cell agarose assay, the immune complexes were shown to inhibit NK cell activity by inhibiting the formation of effector/target cell conjugates.     

Pidotimod Stimulates Natural Killer Cell Activity and Inhibits Thymocyte Cell Death

Experiments were performed to analyze the possible effect of the immunomodulating agent Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) on mouse Natural Killer (NK) cell activity and glucocorticoid hormone(GCH)-induced thymocyte apoptosis. The results indicate that in vivo treatment with Pidotimod (200 mg/Kg ip for 5 days) causes a significant increase in NK activity and in vitro treatment produces a significant reduction of dexamethasone-induced thymocyte apoptosis. This inhibition appears to be dose-dependent and is also evident against TPA or Ca⁺⁺ionophore-induced apoptosis.     

Reduced Natural Killer Cell Activity in Multi-Drug Resistant Pulmonary Tuberculosis

Cellular immune status in five patients with multi-drug resistant pulmonary tuberculosis was investigated and compared with five matched controls with non-resistant tuberculosis. A significant reduction in fresh natural killer (NK)-cell activity was found in the resistant group ( P < 0.005). There were no significant differences between the two groups in lymphocyte phenotype, proliferation or PPD-specific cytotoxicity. Reduced NK-cell function may play a role in the pathogenesis of multi-drug resistant pulmonary tuberculosis.     

Altered Natural Killer Cell Activity in Childhood Acute Non-lymphoid Leukaemia

Peripheral blood and bone marrow mononuclear cells from 25 children with acute non-lymphoid leukaemia were analysed for natural killer cell activity and for cells with the Leu-7 and Leu-11b (CD 16) markers. Significantly reduced spontaneous cytotoxicity was detected in peripheral blood from children with untreated and active acute non-lymphoid leukaemia compared with that of the controls (P = 0.01 and P less than 0.05). Patients in remission, however, had normal natural cytotoxicity and normal numbers of Leu-7 and Leu-11b (CD 16)-positive cells. The natural killer cell activity in bone marrow from patients with untreated acute non-lymphoid leukaemia was also significantly reduced (P = 0.025). On the other hand, patients in remission had both an increased percentage of Leu-7 and Leu-11b (CD 16)-positive cells (P less than 0.05) and an increased natural killer cell activity (P less than 0.0005) in their bone marrow cells in comparison with the control group. This augmented natural killer cell activity is most probably a result of anti-leukaemic treatment. Stimulation with recombinant alpha interferon and recombinant interleukin 2 caused an increase in natural killer cell activity that was both significant and normal in both peripheral blood and bone marrow from children with acute non-lymphoid leukaemia.     

Pidotimod Stimulates Natural Killer Cell Activity and Inhibits Thymocyte Cell Death

Abstract

Experiments were performed to analyze the possible effect of the immunomodulating agent Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) on mouse Natural Killer (NK) cell activity and glucocorticoid hormone(GCH)-induced thymocyte apoptosis. The results indicate that in vivo treatment with Pidotimod (200 mg/Kg ip for 5 days) causes a significant increase in NK activity and in vitro treatment produces a significant reduction of dexamethasone-induced thymocyte apoptosis. This inhibition appears to be dose-dependent and is also evident against TPA or Ca⁺⁺ionophore-induced apoptosis.     

Natural Killer Cell Activity in Multiple Sclerosis and Myasthenia Gravis

Because of the potential role of Natural Killer (NK) cells in viral immunity and immunoregulation, we have undertaken a study of NK activity of peripheral blood lymphocytes from both Multiple Sclerosis (MS) and Myasthenia Gravis (MG) patients, two chronic diseases in which a viral etiology and an induced autoregulatory abnormality are strongly implicated. No significant difference between the mean NK activity in MS patients and controls was observed. A difference was observed between the NK activity of female MG patients and female controls, but no difference was seen between male MG patients and controls.     

Characterization of the in vivo and in vitro Effects of Indomethacin on Human Natural Killer Cell Activity

The in vivo and in vitro effects of indomethacin on the natural killer (NK) cell activity against K 562 target cells were studied. In vivo administration of indomethacin, 3 X 50 mg for 7 days to normal donors did not influence baseline NK cell activity, which means that treatment with prostaglandin (PG) inhibitors can be allowed in studies on NK cell activity of persons with normal PG production. The NK cell activity of fresh mononuclear cells was boosted with pharmacological concentrations of indomethacin in vitro, while frozen cells were not. Our results indicate that indomethacin enhances the NK cell activity in vitro by blocking the prostaglandin production of monocytes, since monocyte depleted effector cells were not boosted by indomethacin.