巨噬细胞极化与动脉粥样硬化

巨噬细胞是动脉粥样硬化过程中最具代表性的炎症细胞。机体通过多个信号通路选择性表达靶基因,使巨噬细胞呈现相应特征性的分子标志物,最终实现不同极性及功能,即促炎的M1型和抗炎的M2型巨噬细胞。MI/M2型巨噬细胞具有可塑性,二者的分化影响着动脉粥样硬化的发展结局。因此,如何控制巨噬细胞介导的炎症反应已成为心血管领域的关注热点,也为动脉粥样硬化的防治带来新的希望。     

巨噬细胞极化在痛风炎症机制中的研究

痛风性关节炎是一种可涉及一系列复杂的炎症级联扩增反应的自身炎症性疾病, 其区别于其他自身炎性关节病的特征之一是其关节炎症在临床上可表现为自发缓解。促炎因子与抗炎因子动态平衡在痛风炎症自发缓解机制中发挥重要作用。巨噬细胞是人体固有免疫细胞, 在不同的微环境下, 巨噬细胞可极化为促炎的M1型与抗炎的M2型, 不同表型之间的转化贯穿于痛风炎症发生、发展和转归过程。促进巨噬细胞M2型极化可以缓解痛风急性炎症, 故早期调控痛风炎症中M1及M2各亚群之间的平衡成为探索痛风急性炎症新治疗策略的重要切入点。     

巨噬细胞极化在心血管疾病中的作用及中药干预研究进展

巨噬细胞具有异质性及可塑性,微环境是影响巨噬细胞表型变化的关键因素。在心血管疾病中,巨噬细胞可随所处的微环境极化为不同表型(M1、M2型等)。它们分别表达不同的表面受体,释放不同的细胞因子,受多种信号通路和转录的调控,在心血管疾病发展中行使不同的功能。其中M1型通过分泌促炎因子,负责启动和维持炎症反应;M2型通过分泌抗炎因子,参与炎症消退和组织修复。中药多具有扶正、活血化瘀、清热解毒之功效,通过调控JAK/STAT、PI3K/Akt、Toll受体等信号通路,减少巨噬细胞聚集,促进巨噬细胞向M2极化或恢复M1/M2之间的动态平衡,以改善炎性微环境,延缓疾病进展。文章主要从巨噬细胞的起源、极化诱导因素及亚型分类、调控机制、巨噬细胞极化在心血管疾病中的作用及中药干预进行系统梳理,为心血管疾病防治提供理论指导。     

肝巨噬细胞调控肝癌癌前病变恶变的研究进展

肝巨噬细胞是肝脏中重要的免疫细胞,其通过极化为M1型和M2型,分别表达“促炎因子”和“抑炎因子”,进而发挥调控炎症损伤反应的作用。肝祖细胞恶变是肝癌癌前病变恶性进展的核心机制,其发生的关键因素是炎症损伤微环境的持续刺激,与M1/M2巨噬细胞极化密切相关。本综述主要围绕“巨噬细胞极化-慢性炎症-肝祖细胞恶变”关系进行探讨,为肝癌癌前病变的预防和治疗提供重要的理论依据。     

巨噬细胞在支气管哮喘中的作用及研究进展

受微环境变化的影响,巨噬细胞分为经典激活的巨噬细胞(M1)和非经典激活的巨噬细胞(M2).M1型巨噬细胞可释放如肿瘤坏死因子α(TNF-α)和IL-1β等促炎因子加重炎症反应,也可因极化的增多发挥抗炎作用.M2型巨噬细胞分为M2a、M2b和M2c 3种亚型,M2a及M2b型巨噬细胞主要产生炎性细胞因子如ID4和IL-13,M2c型巨噬细胞主要产生抗炎细胞因子如IL-10并有很强的吞噬功能.细胞因子、趋化因子和免疫调节细胞影响着M1型和M2型巨噬细胞的平衡.巨噬细胞不同的极化在支气管哮喘发生与发展中起到重要的作用.     

巨噬细胞极化在寄生虫感染中的作用研究进展

巨噬细胞是固有免疫的重要成员,在机体防御病原生物感染、肿瘤、过敏性疾病等发生发展中发挥着极其重要的作用。巨噬细胞具有高度可塑性,在不同环境刺激下巨噬细胞可极化为经典活化型巨噬细胞（M1型巨噬细胞）和替代活化型巨噬细胞（M2型巨噬细胞）。M1型巨噬细胞能够促进机体炎症反应,有利于清除病原体;M2型巨噬细胞能够抑制炎症反应,有利于病原体生存、繁殖。本文综述巨噬细胞极化在寄生虫感染中的作用,为寄生虫病防治研究提供参考。     

间充质干细胞调控巨噬细胞极化在ALI/ARDS中作用的研究进展

急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是由多种原因引起的一种临床急危重症,发展非常迅速,病死率极高。肺泡巨噬细胞M1/M2免疫失衡参与ALI/ARDS的发生发展。间充质干细胞可通过调控巨噬细胞由促炎性M1型向抗炎性M2型极化,抑制下游炎症反应,促进组织修复和再生,达到治疗ALI/ARDS的目的。因此,深入...     

M2型巨噬细胞在COPD发病机制中作用的研究进展

M2型巨噬细胞因其促进炎症消散、组织重塑和纤维化的功能特点被认为广泛地参与到了COPD的发生、发展过程中。研究发现,M2型巨噬细胞可能通过影响 IL-17a、IFN-γ以及CCL18水平来促进肺气肿的发生;不仅如此,M2型巨噬细胞还能通过调节各种炎症因子水平来促进炎症消散,同时还能通过影响 ADORA3水平来参与基质金属蛋白酶的产生、转化生长因子β通路的激活,从而引起小气道病变。但 M2型巨噬细胞参与 COPD发病的分子机制尚未完全明确,本文将对M2型巨噬细胞在COPD发病机制中作用的相关研究进行综述。     

巨噬细胞极化在心肌纤维化中的作用及Notch信号通路相关研究

巨噬细胞是一类免疫功能多样且具有高度异质性的细胞群体,在不同微环境的刺激下,可极化为两个亚群:M1型和M2型,且在心肌纤维化发展不同阶段其极化表型及功能存在显著差异。即在心肌纤维化早期,M1型比例升高以促进炎症进展;在心肌纤维化后期,M2型比例升高以缓解心肌纤维化。Notch信号通路可调控巨噬细胞极化,与心肌纤维化的发展有关,尤其是在心肌梗死、心力衰竭等心血管疾病中。故阻断Notch信号通路有利于调控巨噬细胞极化,进而有助于抑制或逆转心肌纤维化进程。     

巨噬细胞极化与2型糖尿病关系的研究进展

近年来我国T2DM发病率不断升高,严重影响人类健康。T2DM患者巨噬细胞M1/M2极化出现失衡,表现为促炎M1型巨噬细胞增多,抗炎M2型巨噬细胞减少。巨噬细胞极化失衡通过多种途径引起IR或损伤胰岛β细胞,调整巨噬细胞极化对T2DM起治疗作用。本文综述巨噬细胞极化与T2DM关系的研究进展。     

巨噬细胞极化分型与儿童支气管哮喘的相关性分析

目的 探讨巨噬细胞极化分型与儿童支气管哮喘(简称哮喘)演进的相关性并分析其可能相关机制.方法 分离2014年9月至2016年8月两年间西安市儿童医院哮喘患儿外周血中单核巨噬细胞,流式细胞术分析M1与M2的比例,并且分析其与患儿急性发作严重分级的相关性及常规全球哮喘防治创议方案控制疗效的相关性.结果 哮喘患儿急性发作严重分级及控制疗效与外周血中巨噬细胞无相关性(P＞0.05),与M1及M2呈现较强的相关性(P＜0.01),与M1呈正相关(r=0.938),与M2呈负相关(r=-0.835).结论 哮喘患儿外周血中巨噬细胞的不同亚群对该疾病的演进及预后发挥不同的作用,因此巨噬细胞极性的转变有可能成为儿童哮喘治疗的关键节点.     

Interactions of helminths with macrophages: therapeutic potential for inflammatory intestinal disease

ABSTRACT

Introduction: Macrophages represent a highly heterogeneous and plastic cell type found in most tissues of the body; the intestine is home to enormous numbers of these cells. Considerable interest surrounds the ‘M2 macrophage,’ as it is able to control and regulate inflammation, while promoting tissue repair.

Areas covered: As potent inducers of M2 macrophages, intestinal helminths and helminth-derived products are ideal candidates for small molecule drug design to drive M2 macrophage polarization. Several gastrointestinal helminths have been found to cause M2 macrophage-inducing infections. This review covers current knowledge of helminth products and their impact on macrophage polarization, which may in the future lead to new therapeutic strategies.

A literature search was performed using the following search terms in PubMed: M2 macrophage, alternative activation, helminth products, helminth ES, helminth therapy, nanoparticle, intestinal macrophages. Other studies were selected by using references from articles identified through our original literature search.

Expert commentary: While the immunomodulatory potential of helminth products is well established, we have yet to fully characterize many components of the intestinal helminth product library. Current work aims to identify the protein motifs responsible for modulation of macrophages and other components of the immune system.     

Hepcidin Induces M1 Macrophage Polarization in Monocytes or THP-1 Derived Macrophages

Background: Macrophage polarization plays a critical role in determining the inflammatory states. Hepcidin is a key negative regulator of iron homeostasis and functions. Although hepcidin has been shown to affect ferroportin expression in macrophages, whether it affects macrophage polarization is still largely unknown. Objective: To address whether hepcidin induces macrophage polarization. Methods: The expression of iNOS and CD206, and the ratio of IFN-γ vs IL-4 in THP-1 derived macrophages upon hepcidin stimulation were evaluated. Further detected was the percentage of CD16+ M1, CD23+ M1, CD10+ M2 and CCL22+ M2 cells in monocyte derived macrophages. Results: M1 associated molecules were increased in hepcidin-treated cells, yet M2 associated molecules were increased when hepcidin was neutralized. Concomitantly, we observed a significant increase in IRF3 phosphorylation in hepcidin-stimulated cells. However, STAT6 phosphorylation with hepcidin was neutralized. Conclusion: Hepcidin is able to induce macrophage polarization towards M1 type, and might be utilized as a potential M1 macrophage agonist in clinical practice.     

Epigenetic regulation in monocyte/macrophage: A key player during atherosclerosis

Atherosclerosis is a chronic inflammatory disease. Recently, a growing body of evidence emphasizes that the monocyte and macrophage differentiation and activation are key processes in the development of atherosclerosis. However, the regulatory mechanism that manipulates the function of monocyte and macrophage is still unclear. Recent years, epigenetic mechanisms have received a wide attention and bring us a new field of vision. More and more evidence shows that epigenetics weighs heavily in atherosclerosis by regulating the function and differentiation states of monocyte and macrophage. In this review, we illuminate the epigenetic regulation mechanisms in monocyte and macrophage and their contributions to inflammatory processes of atherosclerosis to provide new thoughts and find novel targets or biomarkers for atherosclerosis.     

Sequential Co-infection of Heligmosomoides polygyrus and Mycobacterium tuberculosis Determine Lung Macrophage Polarization and Histopathological Changes

BackgroundTuberculosis is a chronic infection caused by Mycobacterium tuberculosis (M.tb), which needs proper macrophage activation for control. It has been debated whether the co-infection with helminth will affect the immune response to mycobacterial infection.ObjectiveTo determine the effect of sequential co-infection of Heligmosomoides polygyrus (H.pg) nematodes and M.tb on T cell responses, macrophages polarization and lung histopathological changes.MethodThis study used 49 mice divided into 7 treatment groups, with different sequence of infection of M.tb via inhalation and H.pg via oral ingestion for 8 and 16 weeks. T cells response in the lung, intestine, and peripheral blood were determined by flow cytometry. Cytokines (IL-4, IFN-γ, TGB-β1, and IL-10) were measured in peripheral blood using ELISA. Lung macrophage polarization were determined by the expression of iNOS (M1) or Arginase 1 (M2). Mycobacterial count were done in lung tissue. Lung histopathology were measured using Dorman’s semiquantitative score assessing peribronchiolitis, perivasculitis, alveolitis, and granuloma formation.ResultM.tb infection induced Th1 response and M1 macrophage polarization, while H.pg infection induced Th2 and M2 polarization. In sequential co-infection, the final polarization of macrophage was dictated by the sequence of co-infection. However, all groups with M.tb infection showed the same degree of mycobacterial count in lung tissues and lung tissue histopathological changes.ConclusionSequential co-infection of H.pg and M.tb induces different T cell response which leads to different macrophage polarization in lung tissue. Helminth infection induced M2 lung macrophage polarization, but did not cause different mycobacterial count nor lung histopathological changes.     

Macrophage polarization: The answer to the diet/inflammation conundrum?

Macrophages, a heterogeneous and ubiquitous cell population representing up to 15% of the cellular content of different types of tissue, are the principal cell mediators in response to pathogens, inflammation process, tissue homeostasis and repair and play a pivotal role in atherosclerosis and insulin resistance because of their capacity to be the major source of inflammatory cytokines, which can function through paracrine and endocrine mechanisms. Recently, differently activated macrophage populations have been described, depending on a large variety of microenvironmental signals, and it is now recognized that their activation plays a crucial role in the development and progression of atherosclerosis. There is good evidence of the ability of conjugated linoleic acids and polyphenolic compounds to modulate inflammation in experimental models involving macrophages. This observation leaves room to the intriguing hypothesis that macrophage polarization could represent one of the unifying mechanisms through which specific food components can exert anti-inflammatory effects in humans, contributing to the prevention of chronic diseases strongly linked to inflammation, such as atherosclerosis. Future studies should be addressed to substantiate this hypothesis, investigating whether or not physiological concentrations of food-derived metabolites can perturb macrophage activation in vitro. On the in vivo side, the evaluation of macrophage populations in tissues, however complex, should be included among the analyses performed in observational and intervention studies, in order to understand if macrophage activation is involved in the anti-inflammatory activity of a specific dietary regimen.     

巨噬细胞极化机制及其在常见疾病中的作用

巨噬细胞是人体天然免疫系统的重要组成部分，具有高度的可塑性，可在不同的微环境信号刺激下分化为具有促炎作用的经典活化型巨噬细胞（classical activated macrophage，M1型）和具有抗炎作用的选择性活化型巨噬细胞（alternative activated macrophage，M2型）。巨噬细胞的极化涉及许多信号通路和转录因子的调控，且M1/M2表型与肿瘤、Ⅱ型糖尿病、重症急性胰腺炎等疾病的发生发展有关。本文通过介绍与巨噬细胞极化有关的主要信号通路及常见疾病中巨噬细胞的极化状态，明确巨噬细胞的极化平衡在维持人体稳态中的重要作用，以期为相关临床研究提供新思路。     

Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques

Macrophages, a significant component of atherosclerotic plaques vulnerable to acute complications, can be pro-inflammatory (designated M1), regulatory (M2), lipid- (Mox) or Heme-induced (Mhem). We showed previously that low (LSS) and oscillatory (OSS) shear stress cause thin-cap fibroatheroma and stable smooth muscle cell-rich plaque formation respectively in ApoE-knockout (ApoE^−/−) mice. Here we investigated whether different shear stress conditions relate to specific changes in macrophage polarization and plaque morphology by applying a shear stress-altering cast to the carotid arteries of high fat-fed ApoE^−/− mice. The M1 markers iNOS and IRF5 were highly expressed in macrophage-rich areas of LSS lesions compared to OSS lesions 6 weeks after cast placement, while the M2 marker Arginase-1, and Mox/Mhem markers HO-1 and CD163 were elevated in OSS lesions. Our data indicates shear stress could be an important determinant of macrophage polarization in atherosclerosis, with low shear promoting M1 programming.