巨噬细胞的三种活化

IFN-γ诱导产生、经典活化的巨噬细胞参与Th1型免疫应答,对细胞内感染病原体如结核杆菌有很好杀伤作用。由IL-4、IL-13等所诱导的替代性活化的巨噬细胞,具有组织修复功能,是与经典活化的巨噬细胞不同的表现型。近来研究表明,FcγRs与其配体结合所诱导活化的巨噬细胞——Ⅱ型活化的巨噬细胞与上述两种活化的巨噬细胞不同,具有抗炎症并参与,Th2型免疫应答的作用。该主要讨论这三种类型活化的巨噬细胞的发现、活化的信号及其生物学功能。     

巨噬细胞极化及其在慢性阻塞性肺疾病中的作用

巨噬细胞具有高度可塑性,在炎症因子的诱导和多种信息分子的调控下可极化为经典活化巨噬细胞(M1)和替代活化巨噬细胞(M2)。慢性肺部炎症反应和肺实质损伤是慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)的主要病理表现。M1促进肺部炎症反应;M2抑制炎症反应,参与肺组织损伤与修复,并吞噬和清除病原微生物和凋亡细胞。靶向干预巨噬细胞极化方向有可能成为COPD治疗的新策略。     

巨噬细胞的分类及其调节性功能的差异

巨噬细胞在固有免疫和适应性免疫反应中具有重要的作用,它可将加工后的抗原提呈给相应的T细胞,活化后的T细胞通过细胞膜上的分子或分泌的细胞介素进一步活化巨噬细胞。此时的巨噬细胞吞噬杀伤能力大大加强,并释放各种活性物质,因此巨噬细胞是主要的炎性反应调节细胞。巨噬细胞可分为经典活化和选择性活化的巨噬细胞,其在炎性反应过程中分泌不同的细胞因子、趋化因子等,然后间接或直接地参与各种炎症性疾病的反应过程。该文介绍了不同型巨噬细胞在胰岛素抵抗、HIV感染和肿瘤等疾病中的调节功能。     

巨噬细胞极化在类风湿关节炎中的作用

类风湿关节炎(rheumatiod arthritis,RA)是侵犯骨和关节为主的多系统炎症的自身免疫性疾病。巨噬细胞具有吞噬?趋化?免疫调节等功能,参与特异性和非特异性免疫应答,其在RA的发生发展中起到至关重要的作用。巨噬细胞不同亚型极化及其作用是近年来RA的致病机制的研究热点。巨噬细胞主要分为经典活化M1型和选择活化M2型。RA患者机体内免疫炎症反应直接影响外周血、滑膜和滑液巨噬细胞的极化,使M1型促炎性巨噬细胞不断增加,从而打破M1/M2平衡状态。现总结巨噬细胞的极化及其在RA发生发展中的作用?     

低氧诱导脂肪组织纤维化的研究进展

肥胖状态下,白色脂肪组织持续扩张引起组织缺氧,激活低氧诱导因子1α(HIF-1α)。HIF-1α可刺激纤维化基因表达,启动脂肪组织纤维化进程。脂肪组织纤维化可募集和活化M1型巨噬细胞,导致脂肪组织慢性炎症。HIF-1α还可同时刺激炎症基因表达,进而募集和活化M1型巨噬细胞,引起脂肪组织慢性炎症。脂肪组织慢性炎症又进一步促进了脂肪组织纤维化的发展。脂肪组织纤维化促使过量的甘油三酯异位沉积于肝脏等内脏组织,导致多种代谢性疾病的发生发展。     

血液系统恶性疾病中巨噬细胞的研究进展

巨噬细胞是微环境中重要成员,其表型、功能具有很强的异质性;近年的研究不仅揭示了稳态条件下不同亚群的形态、表型及功能特点,而且逐步阐明疾病状态下巨噬细胞的变化及作用机制.肿瘤微环境中的巨噬细胞称为肿瘤相关巨噬细胞(T A M s),参与肿瘤增殖、血管生成、浸润、转移及化疗抵抗.在血液系统恶性疾病中,巨噬细胞广泛浸润到淋巴瘤、骨髓瘤、白血病等恶性细胞累及的组织中,被恶性微环境异常活化,获得了特异的活化表型,并参与疾病进展.在淋巴瘤、骨髓瘤中习惯沿用T A M s的名称;在白血病中其名称引申为白血病相关巨噬细胞、急性白血病相关巨噬细胞或者"保姆样细胞".本文综述了血液系统恶性疾病中巨噬细胞的研究进展.     

羊骨胶原肽对大鼠腹腔巨噬细胞免疫能力的影响

目的 探究羊骨胶原肽(sheep bone collagen peptide,SBCP)对正常状态及脂多糖(lipopolysaccharide,LPS)活化状态巨噬细胞免疫能力的影响.方法 以不同剂量的SBCP作用于未经LPS活化和LPS活化的大鼠腹腔巨噬细胞,分别以MTT法和中性红法测定巨噬细胞代谢活力和吞噬活性,...     

巨噬细胞的极化及其意义

表型可变性和功能多样性是单个核吞噬细胞的重要特征。近年来巨噬细胞的极化受到关注。一般认为极化巨噬细胞是单核细胞活化后一系列功能状态两个极端。而它的分化受到各种微环境信号的诱导与调节。极化的巨噬细胞能够进一步影响局部免疫反应,与各种因子协同作用调节病原体微生物感染结局和肿瘤免疫,参与免疫调节,组织修复重塑过程。对巨噬细胞亚型诱导因素及功能的研究将有助于了解免疫反应的调节机制。     

衣康酸修饰的化学蛋白质组学分析

衣康酸是近年来被发现的参与到病原体-宿主相互作用中的炎症调控代谢物。衣康酸由于其亲电性可以共价修饰蛋白质中的半胱氨酸，从而调控底物蛋白的功能并介导其在巨噬细胞中的抗炎活性。目前，科学家们利用化学蛋白质组学技术大规模地鉴定了巨噬细胞与病原菌中的衣康酸修饰蛋白及位点，揭示了衣康酸修饰在糖酵解、细胞死亡和炎性小体活化等过程中的重要调控作用。现就衣康酸修饰生物学功能及其化学蛋白质组学分析方法的研究进展进行综述，并对该领域的研究难点进行探讨和展望。     

小胶质细胞在帕金森病病理进展中的作用

帕金森病是中老年人常见的中枢神经系统退行性疾病,研究表明小胶质细胞的活化及其介导的神经炎症在帕金森病的病程进展中发挥重要作用,适度干预小胶质细胞的活化有望延缓帕金森病的进程。小胶质细胞是中枢神经系统固有的巨噬细胞,Notch信号途径可以调控小鼠外周巨噬细胞的分化及功能。Notch通路也参与调控小胶质细胞的激活、细胞因子的表达、吞噬活性的变化等,而这与活化的小胶质细胞介导的帕金森病等神经退行性疾病的病情进展相关。因此,本文将综述Notch信号途径与小胶质细胞介导的相关疾病的研究进展。     

Unfolding the relationship between secreted molecular chaperones and macrophage activation states

Over the last 20 years, it has emerged that many molecular chaperones and protein-folding catalysts are secreted from cells and function, somewhat in the manner of cytokines, as pleiotropic signals for a variety of cells, with much attention being focused on the macrophage. During the last decade, it has become clear that macrophages respond to bacterial, protozoal, parasitic and host signals to generate phenotypically distinct states of activation. These activation states have been termed ‘classical’ and ‘alternative’ and represent not a simple bifurcation in response to external signals but a range of cellular phenotypes. From an examination of the literature, the hypothesis is propounded that mammalian molecular chaperones are able to induce a wide variety of alternative macrophage activation states, and this may be a system for relating cellular or tissue stress to appropriate macrophage responses to restore homeostatic equilibrium.     

Molecular mechanisms of regulation of the macrophage activity

This review systematized modern conceptions of the most frequently occurring types of macrophage activation. Mechanisms of induction and regulation of these three types of activation were discussed. Any macrophage population was shown to easily change its properties depending on its microenvironment and concrete biological situation (functional plasticity of macrophages). Many intermediate functional states of macrophages were described, along with the most pronounced and well-known activation states (classical activation, alternative activation, and type II activation). These intermediate states were characterized by various compositions of their biological properties, including elements of all the three aforementioned types of activation. Macrophage activity was shown to be regulated by a complex network of interrelated cascade mechanisms.     

Mitochondrial metabolism regulates macrophage biology

Mitochondria are critical for regulation of the activation, differentiation, and survival of macrophages and other immune cells. In response to various extracellular signals, such as microbial or viral infection, changes to mitochondrial metabolism and physiology could underlie the corresponding state of macrophage activation. These changes include alterations of oxidative metabolism, mitochondrial membrane potential, and tricarboxylic acid (TCA) cycling, as well as the release of mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA) and transformation of the mitochondrial ultrastructure. Here, we provide an updated review of how changes in mitochondrial metabolism and various metabolites such as fumarate, succinate, and itaconate coordinate to guide macrophage activation to distinct cellular states, thus clarifying the vital link between mitochondria metabolism and immunity. We also discuss how in disease settings, mitochondrial dysfunction and oxidative stress contribute to dysregulation of the inflammatory response. Therefore, mitochondria are a vital source of dynamic signals that regulate macrophage biology to fine-tune immune responses.     

Molecular mechanisms regulating the activity of macrophages

This article reviews modern concepts of the most common types of macrophage activation: classical, alternative, and type II. Molecular mechanisms of induction and regulation of these three types of activation are discussed. Any population of macrophages was shown to change its properties depending on its microenvironment and concrete biological situation (the "functional plasticity of macrophages"). Many intermediate states of macrophages were described along with the most pronounced and well-known activation types (classical activation, alternative activation, and type II activation). These intermediate states are characterized by a variety of combinations of their biological properties, including elements of the three afore mentioned types of activation. Macrophage activity is regulated by a complex network of interrelated cascade mechanisms.     

Tumor associated macrophages and neutrophils in tumor progression

Tumor‐associated macrophages (TAMs) are a key component of the tumor microenvironment and orchestrate various aspects of cancer. Diversity and plasticity are hallmarks of cells of the monocyte–macrophage lineage. In response to distinct signals macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a spectrum of activation states. Metabolic adaptation is a key component of macrophage plasticity and polarization, instrumental to their function in homeostasis, immunity and inflammation. Generally, TAMs acquire an M2‐like phenotype that plays important roles in many aspects of tumor growth and progression. There is now evidence that also neutrophils can be driven towards distinct phenotypes in response to microenvironmental signals. The identification of mechanisms and molecules associated with macrophage and neutrophil plasticity and polarized activation provides a basis for new diagnostic and therapeutic strategies. J. Cell. Physiol. 228: 1404–1412, 2013. © 2012 Wiley Periodicals, Inc.     

Metabolic Characterization of Leishmania major Infection in Activated and Nonactivated Macrophages

Infection with Leishmania spp. can lead to a range of symptoms in the affected individual, depending on underlying immune-metabolic processes. The macrophage activation state hereby plays a key role. Whereas the l-arginine pathway has been described in detail as the main biochemical process responsible for either nitric oxide mediated parasite killing (classical activation) or amplification of parasite replication (alternative activation), we were interested in a wider characterization of metabolic events in vitro. We therefore assessed cell growth medium, parasite extract, and intra- and extracellular metabolome of activated and nonactivated macrophages, in presence and absence of Leishmania major. A metabolic profiling approach was applied combining (1)H NMR spectroscopy with multi- and univariate data treatment. Metabolic changes were observed along both conditional axes, that is, infection state and macrophage activation, whereby significantly higher levels of potential parasite end products were found in parasite exposed samples including succinate, acetate, and alanine, compared to uninfected macrophages. The different macrophage activation states were mainly discriminated by varying glucose consumption. The presented profiling approach allowed us to obtain a metabolic snapshot of the individual biological compartments in the assessed macrophage culture experiments and represents a valuable read out system for further multiple compartment in vitro studies.     

Macrophage–Cryptococcus Interactions: An Update

Cryptococcus species are fungal pathogens that are a leading cause of mortality. Initial inoculation is through the pulmonary route and, if disseminated, results in severe invasive infection including meningoencephalitis. Macrophages are the dominant phagocytic cell that interacts with Cryptococcus. Emerging theories suggest that Cryptococcus microevolution in macrophages is linked to survival and virulence within the host. In addition, Cryptococcus elaborates virulence factors as well as usurps host machinery to establish macrophage activation states that are permissive to intracellular survival and replication. In this review, we provide an update of the recent findings pertaining to macrophage interaction with Cryptococcus and focus on new avenues for biomedical research.