滤泡淋巴瘤新靶向药物治疗机制与临床选择

滤泡淋巴瘤是最常见的惰性淋巴瘤,目前常用免疫化疗方案治疗,但进展及复发患者预后较差。新靶向药物包括细胞表面抗体、免疫调节剂、细胞信号通路激酶抑制剂、嵌合抗原受体T细胞疗法、树突细胞疫苗等显著延长患者的生存期,为临床治疗提供新的选择。     

Human phagocytic cell response to histamine derived from potential probiotic strains of Lactobacillus reuteri

Histamine derived from lactobacilli isolates is considered to be a potential immunomodulator able to interact with the host immune system. We tested the effect of pure histamine (0.413?mM) together with the effect of cell-culture supernatants (CCS) containing different concentration of histamine produced by two of Lactobacillus reuteri isolates on the activities of antioxidant enzyme, as well as on the phagocytic activity of human leucocytes (HL). Phagocytic activity represents the non-specific immune response of HL homogenate, in vitro. Analysed histamine-producers were represented by a goatling isolate named L. reuteri KO5 and a lamb isolate named L. reuteri E and histamine production was determined using HPLC method connected with UV detection. Concretely, the samples contained the mixture of isolated HL and the addition of lactobacilli CCS at three different final concentrations of histamine ～ 0.1, 1.8 and 5.4?mM. It was found that pure histamine (0.413?mM) did not significantly influence the oxidant-antioxidant balance in HL demonstrated by unchanged degree of HL lipid peroxidation. However, at the same time, the final activity of catalase and superoxide dismutase were significantly changed (p?≤?0.001).Moreover, the phagocytic index (p?≤?0.01), lysozyme (p?≤?0.05) and peroxidase activity (p?≤?0.001), and production of IL-1β significantly decreased. CCS containing different concentration of produced histamine were also able to modulate the host non-specific immune response together with the enzymatic activity of SOD and catalase too. However, our findings indicated that the impact of lactobacilli histamine is strictly strain-dependent and concentration dependent. Moreover, it seems that histamine is not the only one lactobacilli metabolite, which may play an important role in overall immunomodulatory and antioxidant potential of tested lactobacilli.     

Immunomodulatory effects of mesenchymal stem cells on leukocytes with emphasis on neutrophils

Mesenchymal stem cells (MSCs) are a population of multipotent cells with the ability of expansion and plastic-adherence in vitro. MSCs can differentiate into chondrocytes, osteocytes and adipocytes; they lack co-stimulatory molecules and have small amount of MHC-I that makes no immunogenicity. These characteristics are empowering MSCs’ huge in vivo applications. In addition, MSCs possess the ability of regulating the immune responses in many diseases. Many studies have shown that MSCs have immunosuppressive as well as immunoenhancing properties such as inhibition of T-lymphocytes proliferation and cytokines production which lead to the balance of Th1 and Th2. Some other immunomodulatory features of MSCs are increasing suppressive capacity of T_reg, reducing activity of B-lymphocytes and immunoglobulins secretion, inhibition of dendritic cells maturation and antigen presenting capacity, and inhibition of NK-cells activity. MSCs also exert inhibitory effects on neutrophil apoptosis and reduce reactive oxygen species production. The purpose of this paper is to focus on the MSCs? effects on immune cells, especially neutrophils.     

New immunomodulatory role of neuropeptide Y (NPY) in Salmo salar leucocytes

Neuropeptide Y (NPY) plays different roles in mammals such as: regulate food intake, memory retention, cardiovascular functions, and anxiety. It has also been shown in the modulation of chemotaxis, T lymphocyte differentiation, and leukocyte migration. In fish, NPY expression and functions have been studied but its immunomodulatory role remains undescribed. This study confirmed the expression and synthesis of NPY in S. salar under inflammation, and validated a commercial antibody for NPY detection in teleost. Additionally, immunomodulatory effects of NPY were assayed in vitro and in vivo. Phagocytosis and superoxide anion production in leukocytes and SHK cells were induced under stimulation with a synthetic peptide. IL-8 mRNA was selectively and strongly induced in the spleen, head kidney, and isolated cells, after in vivo challenge with NPY. All together suggest that NPY is expressed in immune tissues and modulates the immune response in teleost fish.     

Vinpocetine Inhibited the CpG Oligodeoxynucleotide-induced Immune Response in Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) exert dual roles in immune responses through inducing inflammation and maintaining immune tolerance. A switch of pDC phenotype from pro-inflammation to tolerance has therapeutic promise in the treatment of autoimmune diseases. Vinpocetine, a vasoactive vinca alkaloid extracted from the periwinkle plant, has recently emerged as an immunomodulatory agent. In this study, we evaluated the effect of vinpocetine on phenotype of pDCs isolated from C57BL/6 mice and explored its possible mechanism. Our data showed that vinpocetine significantly downregulated the expression of CD40, CD80, and CD86 on pDCs and increased the expression of translocator protein (TSPO), the specific receptor of vinpocetine, in pDCs. Vinpocetine significantly inhibited the Toll-like receptor 9 signaling pathway and reduced the secretion of related cytokines in pDCs through TSPO. Furthermore, viability of pDCs was significantly promoted by vinpocetine. These findings imply that vinpocetine serves as an immunomodulatory agent for pDCs and may be applied for the treatment of pDCs-related autoimmune diseases.     

DN Treg细胞发挥免疫调节机制的研究进展

免疫系统是人体的防御系统.αβTCR+CD3+CD4-CD8-NK1.1-双阴性调节性T细胞是新近在人类和啮齿动物模型中发现的一种特殊类型的T淋巴细胞.近年来人们通过实验证实DN Treg细胞可以通过各种途径杀伤抗原特定细胞或肿瘤细胞,使得免疫治疗成为研究热点.DN Treg细胞在免疫调节、免疫抑制、自身免疫性以及抗宿主反应、HIV感染以及抗肿瘤方面有重要作用.本文主要介绍DN Treg细胞在免疫治疗中的进展情况.     

西洋参多糖对钴-60辐照小鼠的免疫调节作用

目的探讨西洋参多糖对钴-60γ射线照射致小鼠免疫抑制模型的免疫调节作用,并初步探讨其作用机制。方法将180只6～8周龄、18～22 g的雌性BALB/c小鼠随机分为5组:空白对照组、模型对照组和3个西洋参多糖剂量组(50mg/kg BW、100mg/kg BW和200mg/kg BW)。除空白对照组外,其余4组于d45,一次性接受全身照射(γ射线总剂量为4Gy)。3 d后,测定脾脏T淋巴细胞增殖能力、迟发型变态反应程度和碳粒廓清实验,测定血清丙二醛水平、超氧化物歧化酶活性和谷胱甘肽过氧化物酶活性。结果西洋参多糖在3个剂量组均能明显升高小鼠T淋巴细胞的增殖能力和迟发型变态反应程度,在100mg/kg BW和200mg/kg BW组能明显增高小鼠碳粒廓清指数,在3个剂量组均能明显降低小鼠血清中MDA水平,在50mg/kg BW组能明显增高小鼠血清SOD活性,小鼠血清GSH-Px活性差异无统计学意义。结论西洋参多糖能增强钴-60γ射线照射致免疫抑制小鼠免疫功能,可能通过减轻氧化应激对免疫系统的损害来实现。     

厄贝沙坦对电压依赖性的Kv1.3和Kv1.5通道电流的阻断作用

目的通过观察厄贝沙坦对电压依赖性的Kv1.3和Kv1.5的阻断作用,探讨厄贝沙坦对此类通道的阻断可能具有的临床作用。方法使用双电极电压钳技术记录表达于非洲爪蟾卵母细胞的Kv1.3和Kv1.5钾通道电流,不同浓度厄贝沙坦灌流对其电流的影响。结果①厄贝沙坦浓度依赖性的阻断Kv1.3通道,阻断的IC50是2.46μmol/L,且阻断具有电压依赖性。②厄贝沙坦浓度依赖性的阻断Kv1.5通道,阻断的IC50是0.47μmol/L,且阻断具有显著的电压依赖性。结论厄贝沙坦阻断开放状态的Kv1.3可能是其发挥免疫调节和抗动脉粥样硬化作用的机制之一;而对开放状态的Kv1.5的阻断可能是其具备减少心房颤动发生率的作用机制之一。