基于LAPS芯片的味觉感受细胞敏感和传导的研究

味觉感受细胞为味觉感受器,表达了酸、甜、苦、咸和鲜味感受受体或离子通道。在味质刺激下,味觉感受细胞发放动作电位并释放神经递质。其时域放电模式编码了味觉信息。最常用的膜片钳技术不利于对味觉细胞的时域放电进行长期无损记录。本研究利用LAPS芯片,对味质刺激下味觉细胞的胞外电位进行无损的长时程记录。另外,利用LAP芯片可寻址的优点,在芯片表面沉积对5-HT敏感的PVC膜,对味觉组织在味质刺激下释放的神经递质5-HT进行测量。实验结果发现,不同类型的味觉细胞对相应味质刺激的响应是可以区分开的,且味觉组织在酸或苦甜鲜刺激下,有神经递质5-HT释放。另外,LAPS芯片为味觉细胞的味觉敏感和传导的研究提供了一种新的方法。     

Study of the Mechanism for in Vitro Activation of Mouse NK Cells by Interferon

The enhancement of the lytic capacity of mouse splenic 'natural killer' (NK) cells by interferon has been studied in vitro as a model for NK cell differentiation from inactive immediate precursors. We show that the increased cytotoxicity is a function of interferon concentration, and that two stages in the NK cell differentiation pathway can be distinguished. The first, very brief, can he performed at 0°C and without protein synthesis and probably corresponds to the fixation of interferon on its cell surface receptors. The second, resulting from the inductive signal given by interferon, proceeds for several hours and requires both RNA and protein synthesis. Our results also indicate that target cells for interferon-induced cytotoxicity are cells for interferon-induced cytotoxicity arc cells with 'null' characteristics, similar to the mature NK cells. Finally, they suggest that no soluble Intermediary factor other than interferon is involved in the enhancing of NK cell cytotoxicity.     

Direct Effects of Activin A on the Activation of Mouse Macrophage RAW264.7 Cells

Macrophages play critical roles in innate immune and acquired immune v/a secreting pro-inflammatory mediators, phagocytosing microorganisms and presenting antigens. Activin A, a member of transforming growth factor （TGF-β） superfamily, is produced by macrophages and microglia cells. In this study, we reported a direct effect of activin A as a pro-inflammatory factor on mouse macrophage cell line RAW264.7 cells. Our data revealed that activin A could not only increase IL-1β and IL-6 production from RAW264.7 cells, but also promote pinocytic and phagocytic activities of RAW264.7 cells. In addition, activin A obviously up-regulated MHC Ⅱ expression on the surface of RAW264.7 cells, whereas did not influence MHC I expression. Activin A also enhanced CD80 expression, which is a marker of activated macrophages, but did not influence RAW264.7 cell proliferation. These data suggest that activin A may regulate primary macrophage-mediated innate and acquired immune response via promoting the activation of rest macrophages.     

Activation of Natural Killer Cells in Arthritis-Susceptible but Not Arthritis-Resistant Mouse Strains following Borrelia burgdorferi Infection

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.     

肝纤维化中星状细胞信号转导通路

肝星状细胞活化增殖是肝纤维化发生的关键。肝星状细胞在活化增殖过程中受多种细胞因子或蛋白的调控,通过表面受体激活信号转导网络系统,促使肝纤维化的发生发展。这些表面受体和信号转导通路成为研究的靶向,为纤维化的发生和逆转提供理论依据。     

中枢神经细胞信号转导可被体外调控

本文主要介绍了精神病药物治疗的困惑,中枢神经细胞信号转导可被体外调控,调序仪对人脑发挥的整体调序作用,整体调序治疗的临床意义。     

Memory B Cells in Mouse Models

One of the principles behind vaccination, as shown by Edward Jenner in 1796, and host protection is immunological memory, and one of the cells central to this is the antigen‐experienced memory B cell that responds rapidly upon re‐exposure to the initiating antigen. Classically, memory B cells have been defined as progenies of germinal centre (GC) B cells expressing isotype‐switched and substantially mutated B cell receptors (BCRs), that is, membrane‐bound antibodies. However, it has become apparent over the last decade that this is not the only pathway to B cell memory. Here, we will discuss memory B cells in mice, as defined by (1) cell surface markers; (2) multiple layers; (3) formation in a T cell–dependent and either GC‐dependent or GC‐independent manner; (4) formation in a T cell–independent fashion. Lastly, we will touch upon memory B cells in; (5) mouse models of autoimmune diseases.     

Protein Tyrosine Kinase Activation and Protein Kinase C Translocation Are Functional Components of CD40 Signal Transduction in Resting Human B Cells

CD40 is a 47kD glycoprotein expressed on all B cells that plays an important role in B cell development and activation. Previous investigations have focused on signal transduction events in activated B cells and B cell lines, and little information is available regarding CD40 signal transduction in resting, normal B cells. Because CD40 plays a critical role in the regulation and activation of resting B cells, we studied the signaling mechanisms involved in functional responses to CD40 ligation in these cells. Treatment of dense tonsil B cells with either protein tyrosine kinase (PTK) or protein kinase C (PKC) inhibitors, but not with an inhibitor of cyclic nucleotide dependent kinases, resulted in abrogation of CD40-mediated cell adhesion, suggesting a role for both PTK and PKC in CD40-mediated B cell adhesion. Direct evidence for CD40-mediated PTK activation was demonstrated by increased tyrosine phosphorylation as detected by anti-phosphotyrosine Western blots of cell lysates prepared from dense resting tonsil B cells stimulated with biotinylated anti-CD40 monoclonal antibody plus avidin. CD40 engagement also resulted in PKC activation, as detected by translocation of cytosolic PKC activity to the membrane-bound compartment. CD40-mediated PKC translocation was dependent on PTK activation, whereas PTK activity induced by CD40 ligation was independent of PKC activity, suggesting that PTK activation precedes PKC activation in resting B cells stimulated with anti-CD40 mAb. The results of our experiments identify PTK and PKC activation as components of CD40 signal transduction in normal, resting B cells and establish a functional role for these events.     

Protein Tyrosine Kinase Activation and Protein Kinase C Translocation Are Functional Components of CD40 Signal Transduction in Resting Human B Cells

CD40 is a 47kD glycoprotein expressed on all B cells that plays an important role in B cell development and activation. Previous investigations have focused on signal transduction events in activated B cells and B cell lines, and little information is available regarding CD40 signal transduction in resting, normal B cells. Because CD40 plays a critical role in the regulation and activation of resting B cells, we studied the signaling mechanisms involved in functional responses to CD40 ligation in these cells. Treatment of dense tonsil B cells with either protein tyrosine kinase (PTK) or protein kinase C (PKC) inhibitors, but not with an inhibitor of cyclic nucleotide dependent kinases, resulted in abrogation of CD40-mediated cell adhesion, suggesting a role for both PTK and PKC in CD40-mediated B cell adhesion. Direct evidence for CD40-mediated PTK activation was demonstrated by increased tyrosine phosphorylation as detected by anti-phosphotyrosine Western blots of cell lysates prepared from dense resting tonsil B cells stimulated with biotinylated anti-CD40 monoclonal antibody plus avidin. CD40 engagement also resulted in PKC activation, as detected by translocation of cytosolic PKC activity to the membrane-bound compartment. CD40-mediated PKC translocation was dependent on PTK activation, whereas PTK activity induced by CD40 ligation was independent of PKC activity, suggesting that PTK activation precedes PKC activation in resting B cells stimulated with anti-CD40 mAb. The results of our experiments identify PTK and PKC activation as components of CD40 signal transduction in normal, resting B cells and establish a functional role for these events.     

弱酸弱硷对小鼠皮肤导电性的影响

本文研究了弱酸、弱碱对小鼠离体皮肤导电性的影响,结果表明,能使细胞内pH值下降的弱酸(二氧化碳)或弱酸盐(醋酸钠)可使皮肤导电性下降,而能婕细胞内pH增高的弱碱(氯化铵)则能使皮肤导电性增加。讨论了这些结果与表皮缝隙连接偶连状态间的可能连系。     

儿茶酚胺对培养的小鼠皮肤导电性和表皮缝隙连接的影响

在培养的小鼠皮肤上研究了儿茶酚胺类物质对皮肤导电性和表皮缝隙连接的影响，主要结果为：（１）在适当浓度下，肾上腺素和异丙肾上腺素均可使皮肤导电性增加，而浓度过高时，肾上腺素则使皮肤导电性下降；（２）仅当皮肤与肾上腺素培养一定时间之后，才能显示显示导电性增加的反应；（３）肾上腺素类物质使皮肤导电性增加的作用需要有谷氨酰胺存在；（４）肾上腺素使皮肤导电性增加的实验条件也能使表皮缝隙连接的面数密度显著增加