白细胞间质素-1不止一种

白细胞间质素[Interleukin-l(IL-1)]以淋巴细胞活化因子,B-细胞活化因子,白细胞内源介体、内源热原和单核细胞因子等不同的名称见诸于书刊。IL-1由活化的巨噬细胞合成和分泌,可刺激免疫和炎症反应。诸如淋巴细胞活化、发热、肝细胞功能、从骨髓中产生和释放嗜中性白细胞及结缔组织细胞增生均由IL-1调节。     

间充质干细胞调节炎症反应的研究进展

间充质干细胞(MSCs)因具有免疫调理、分泌细胞因子和取材方便等优点而备受关注,成为细胞治疗的理想种子细胞。MSCs在炎症反应进程中起着重要调节作用,可通过与炎症细胞的相互作用来调节炎症反应,包括减弱中性粒细胞和淋巴细胞黏附于内皮细胞的能力、调节巨噬细胞向促进炎症的M1型和抑制炎症的M2型巨噬细胞之间的相互转化、调节促进炎症的T细胞与抗炎作用的调节性T细胞(Tregs)之间的平衡等机制来调节炎症反应。炎性环境中,MSCs能够通过自身肿瘤坏死因子α刺激基因6的高表达来抵御炎性环境。不同的炎性介质作用于MSCs,可使其呈现出不同的促炎或抗炎特性,可为众多炎症性疾病的治疗提供了新思路和方法。     

CD28协同刺激信号传导的研究进展

T细胞表面分子CD28介导的协同刺激信号在T细胞的激活、增殖、抗凋亡及促进多种细胞因子的分泌中起重要作用。有关其活化信号在T细胞内的传导巳成为免疫研究的热点,近年的研究表明,CD28在T细胞内可通过多种信号传导分子,如P13K、GRB2、A-SMase、PKC-θ等传导活化信号,亦可通过ITK、MKP等传导活化抑制信号,从而调控T细胞的活化,增殖等作用。     

B细胞刺激因子

<正> B细胞被抗原或抗Ig抗体等物质激活后增殖,并分化为大量分泌抗体的浆细胞。此乃体内抗体的唯一来源。足见B细胞在体液免疫应答中占有的重要位置。因此,B细胞的功能状态及其调节因素甚受医学界重视。B细胞的活化过程是一个受多种因素调节的连续而又复杂的过程,其中最重要的直接影响为T细胞和巨噬细胞产生的淋巴因子和单核因子的刺激作用。     

T细胞应答的代谢特征研究进展

T细胞是参与适应性免疫应答的重要组分之一,它们通过分泌细胞因子或是直接杀伤靶细胞等发挥免疫学功能。未致敏T细胞在参与免疫应答时,会由初始T细胞活化为效应T细胞,之后则发生凋亡或转化为记忆T细胞。研究表明,T细胞的能量代谢方式与其活化与分化有着紧密的联系。不同分化阶段与不同亚群的T细胞在行使其免疫功能时具有不同的代谢特点,并由相关的信号通路调控。本文就T细胞发育、活化、分化、发挥免疫功能等阶段的代谢调节机制进行了阐述,并探讨了T细胞代谢调节在临床诊断与治疗中的应用。     

巨噬细胞选择性活化的信号通路及其干预措施的研究进展

巨噬细胞在不同环境刺激下分化为经典活化巨噬细胞和选择性活化巨噬细胞,巨噬细胞选择性活化的信号通路包括:JAK/STAT6途径、M2分化成熟的转录调节途径(KLF4的转录调节,PPARs的转录调节)以及Jmjd3表观遗传学调节途径。选择性活化对机体而言是一种保护机制,可以依据上述分子理论予以干预,如:细胞因子、PPARγ完全性激动剂、PPARγ部分性激动剂、微量元素硒以及生活方式等通过IL-4/STAT6/PPARγ途径促进巨噬细胞选择性极化。对巨噬细胞选择性活化的信号通路及其促进措施进行了简述。     

鬼毛针多糖对小鼠细胞免疫功能影响的实验研究

20世纪80年代后多种真菌多糖的抑瘤活性被发现以来,真菌多糖作为一类新型药物引起越来越多的关注,成为一个非常活跃的研究领域。目前已证实多种真菌多糖可以通过激活T淋巴细胞、B淋巴细胞、活化巨噬细胞和NK细胞、激活补体、调节细胞因子分泌等对免疫系统发挥多方面的调节活性[     

PPARs调控巨噬细胞的活化与功能

巨噬细胞是先天性防御病原体的关键组分,它参与炎症的发生和消退,同时也参与了组织的修复。巨噬细胞的多种功能通过不同的活化状态完成,即从经典活化状态到替代性活化状态,再到失活状态。巨噬细胞活化的失调与代谢、炎症和免疫病变有关,调节蛋白控制巨噬细胞的活化可作为新的治疗靶点。主要综述过氧化物酶体增殖物激活受体（PPARs）调控巨噬细胞活化的作用。     

原子力显微镜研究不同刺激条件下T细胞的形态和生物力学特性

T细胞的抗原识别和活化可以直接影响整个免疫应答的性质、效能和结果,在人体免疫反应中具有核心作用.细胞的形态结构和力学特性决定着细胞的功能的发挥.利用原子力显微镜（AFM）从纳米水平和皮牛顿量级探测分析静息的T细胞和不同刺激剂（超抗原SEA和植物凝集素PHA）活化的T细胞的形态结构和生物力学特性.研究发现静息的T细胞呈较为规则的圆形,细胞表面相对光滑均一,活化后细胞高度和体积明显增大,体积增大为静息T细胞的2~3倍,高度增加了约50%,这是T细胞经过刺激剂活化后增殖、分化而增大的表现.同时发现活化后的T细胞表面粗糙度增大,细胞表面形成100 nm~1 μm颗粒状团簇结构.这种微纳结构域的形成与T细胞经过活化后细胞表面分子表达和细胞因子的分泌有关,并且与免疫突触的形成和功能发挥密切关联.经过PHA和SEA活化后的T细胞表面粘附力增大,是静息的T细胞的3-6倍,而细胞硬度明显减小,这种力学特性的变化有利于T细胞与病原体的相关作用从而清除病原体.通过AFM的研究,可以进一步的了解T淋巴细胞形态变化与细胞行为之间的关系,为更好地理解T细胞的结构与功能提供了更多可视化的依据.     

分枝杆菌干扰抗原呈递细胞功能的研究进展

结核分枝杆菌(Mycobacterium tuberculosis,Mtb)为巨噬细胞内寄生菌,诱导宿主产生的免疫应答以细胞免疫应答为主,其中活化的T细胞特别是CD4 T辅助细胞(Th)及其激活调节的巨噬细胞等多种细胞所发挥的免疫机制是机体抗Mtb特异性免疫的关键,决定了胞内Mtb是被清除、还是进一步繁殖并发展为活动性结核抑或静止于胞内处于潜伏状态[1].     

Down-regulation of Stathmin Is Required for the Phenotypic Changes and Classical Activation of Macrophages

Macrophages are important cells of innate immunity with specialized capacity for recognition and elimination of pathogens and presentation of antigens to lymphocytes for adaptive immunity. Macrophages become activated upon exposure to pro-inflammatory cytokines and pathogenic stimuli. Classical activation of macrophages with interferon-γ (IFNγ) and lipopolysaccharide (LPS) triggers a wide range of signaling events and morphological changes to induce the immune response. Our previous microtubule (MT) proteomic work revealed that the stathmin association with MTs is considerably reduced in activated macrophages, which contain significantly more stabilized MTs. Here, we show that there is a global decrease in stathmin levels, an MT catastrophe protein, in activated macrophages using both immunoblotting and immunofluorescent microscopy. This is an LPS-specific response that induces proteasome-mediated degradation of stathmin. We explored the functions of stathmin down-regulation in activated macrophages by generating a stable cell line overexpressing stathmin-GFP. We show that stathmin-GFP overexpression impacts MT stability, impairs cell spreading, and reduces activation-associated phenotypes. Furthermore, overexpressing stathmin reduces complement receptor 3-mediated phagocytosis and cellular activation, implicating a pivotal inhibitory role for stathmin in classically activated macrophages.     

Liposomal delivery of biological response modifiers to macrophages

Macrophages activated to the tumoricidal state can recognize and destroy neoplastic cells and leave normal cells unharmed. Systemic activation of macrophages can be achieved by the intravenous administration of liposomes containing various immunomodulators. Much like any particle, liposomes are cleared from the circulation by phagocytic cells. This passive but specific targeting of immunomodulators to macrophages results in their activation forin vitro andin vivo lysis of tumor cells that can be resistant to conventional therapies.     

Therapeutic effects on experimental metastatic tumor-bearing mice by vaccination with GM-CSF gene-modified and tumor antigen-pulsed macrophages

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Immunological Properties of TtT/M-87 Cell Line Established from Murine Pituitary Tumor-Associated Macrophages

TtT/M-87 cell is a macrophage cell line established from thyrotropic pituitary tumor tissues in mouse. In this paper, we report the immunological properties of M-87 cells as a model of tumor-associated macrophage. Contrasting with resident peritoneal macrophages, M-87 cells constitutively secreted small but significant amounts of TNF-α and IL-1α, which were detectable in both biological assays (cytotoxic activity for L929 and co-mitogenic activity for Con A-induced T cell proliferation, respectively) and ELISA, and produced larger amounts of these cytokines upon stimulation with LPS. They expressed MHC class II molecules on their cell surface without stimulation by IFN-γ. The accessory or antigen-presenting cell activity in antibody-producing response of spleen lymphocytes to sheep red blood cells was shown to be much higher in M-87 cells than normal peritoneal macrophages. In addition, when normal spleen lymphocytes were cultured with allogeneic tumor cells, such as EL-4 and S-180, in the presence of M-87 cells, lymphocytes reactive to stimulator cells were activated to manifest inhibitory effect on the tumor cell growth and also to manifest specific cytotoxic effect on the allogeneic tumor cells. These results show that M-87 cells derived from tumor-associated tissue are activated macrophages and that they are inhibitory to tumor cell growth and augmentative in the induction of T-cell-mediated immune responses.     

Depletion and Reconstitution of Macrophages in Mice

Macrophages are critical players in the innate immune response to infectious challenge or injury, initiating the innate immune response and directing the acquired immune response. Macrophage dysfunction can lead to an inability to mount an appropriate immune response and as such, has been implicated in many disease processes, including inflammatory bowel diseases. Macrophages display polarized phenotypes that are broadly divided into two categories. Classically activated macrophages, activated by stimulation with IFNγ or LPS, play an essential role in response to bacterial challenge whereas alternatively activated macrophages, activated by IL-4 or IL-13, participate in debris scavenging and tissue remodeling and have been implicated in the resolution phase of inflammation. During an inflammatory response in vivo, macrophages are found amid a complex mixture of infiltrating immune cells and may participate by exacerbating or resolving inflammation. To define the role of macrophages in situ in a whole animal model, it is necessary to examine the effect of depleting macrophages from the complex environment. To ask questions about the role of macrophage phenotype in situ, phenotypically defined polarized macrophages can be derived ex vivo, from bone marrow aspirates and added back to mice, with or without prior depletion of macrophages. In the protocol presented here clodronate-containing liposomes, versus PBS injected controls, were used to deplete colonic macrophages during dextran sodium sulfate (DSS)-induced colitis in mice. In addition, polarized macrophages were derived ex vivo and transferred to mice by intravenous injection. A caveat to this approach is that clodronate-containing liposomes deplete all professional phagocytes, including both dendritic cells and macrophages so to ensure the effect observed by depletion is macrophage-specific, reconstitution of phenotype by adoptive transfer of macrophages is necessary. Systemic macrophage depletion in mice can also be achieved by backcrossing mice onto a CD11b-DTR background, which is an excellent complementary approach. The advantage of clodronate-containing liposome-mediated depletion is that it does not require the time and expense involved in backcrossing mice and it can be used in mice regardless of the background of the mice (C57BL/6, BALB/c, or mixed background).     

Involvement of Macrophages in Proliferation of Prostate Cancer Cells Infected with Trichomonas vaginalis

Macrophages play a key role in chronic inflammation, and are the most abundant immune cells in the tumor microenvironment. We investigated whether an interaction between inflamed prostate cancer cells stimulated with Trichomonas vaginalis and macrophages stimulates the proliferation of the cancer cells. Conditioned medium was prepared from T. vaginalis-infected (TCM) and uninfected (CM) mouse prostate cancer (PCa) cell line (TRAMP-C2 cells). Thereafter conditioned medium was prepared from macrophages (J774A.1 cell line) after incubation with CM (MCM) or TCM (MTCM). When TRAMP-C2 cells were stimulated with T. vaginalis, protein and mRNA levels of CXCL1 and CCL2 increased, and migration of macrophages toward TCM was more extensive than towards CM. Macrophages stimulated with TCM produced higher levels of CCL2, IL-6, TNF-α, their mRNAs than macrophages stimulated with CM. MTCM stimulated the proliferation and invasiveness of TRAMP-C2 cells as well as the expression of cytokine receptors (CCR2, GP130, CXCR2). Importantly, blocking of each cytokine receptors with anti-cytokine receptor antibody significantly reduced the proliferation and invasiveness of TRAMP-C2 cells. We conclude that inflammatory mediators released by TRAMP-C2 cells in response to infection by T. vaginalis stimulate the migration and activation of macrophages and the activated macrophages stimulate the proliferation and invasiveness of the TRAMP-C2 cells via cytokine-cytokine receptor binding. Our results therefore suggested that macrophages contribute to the exacerbation of PCa due to inflammation of prostate cancer cells reacted with T. vaginalis.     

Exposure to chemokines during maturation modulates antigen presenting cell function of mature macrophages

Macrophages generated with macrophage-colony stimulating factor (M-CSF) are defective in antigen presenting cell (APC) function, although they do express major histocompatibility (MHC) class II molecules, numerous accessory molecules, and intercellular adhesion molecules. In the present study, we show evidence that the acquisition of APC function is influenced significantly by microenvironmental condition of development. Macrophages generated from bone marrow progenitor cells with M-CSF and interleukin (IL)-6 were defective in APC function as determined by their ability to induce anti-CD3 monoclonal antibody (mAb)-primed T cell proliferation. Macrophages generated in the presence of some of the CC chemokines such as leukotactin-1, macrophage inflammatory protein (MIP)-1alpha, and RANTES together with M-CSF and IL-6, however, induced proliferation of anti-CD3 mAb-primed T cells. Maximum level of APC function was obtained when developing macrophages were exposed with the chemokines at the late stage of maturation. Enhanced APC function of the macrophages appeared to be correlated with the expression of co-stimulatory molecules and the ability to produce cytokines. These results suggest that the acquisition of APC function of mature macrophage is modulated significantly by the microenvironmental condition during development.