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.     

miRNA和lncRNA调控巨噬细胞极化在变应性疾病中的作用

巨噬细胞是免疫系统重要的吞噬细胞及抗原呈递细胞,广泛分布于人体各个组织。巨噬细胞的可塑性极强,组织微环境的变化可使其极化为不同的表型并表现出不同的生物学功能,如经典途径激活的M1促炎型和替代途径激活的M2抗炎型。其中,M2型巨噬细胞在变应性疾病中占主导地位,并与变应性疾病的发生发展密切相关。微小RNA(miRNA)和长链非编码RNA(lncRNA)是巨噬细胞极化及快速重编程中的关键调节因子,miRNA和lncRNA的差异表达可影响巨噬细胞的极化状态及免疫调节能力。本文对miRNA和lncRNA调控巨噬细胞极化在变应性疾病中的作用进行综述,以期为变应性疾病发病机制研究及临床诊治开辟全新的视角。     

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。     

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。     

间充质干细胞上清对高糖慢性炎症损伤的巨噬细胞表型极化的影响

目的探讨脂肪间充质干细胞(MSCs)培养上清对高糖、炎症环境中巨噬细胞表型的影响及其机制。方法分别以及联合利用高浓度葡萄糖(33 mmol/L)、脂多糖(LPS;1μg/ml)体外处理大鼠腹腔巨噬细胞12 h。依据是否采用MSCs干预分为干预组和非干预组,考察各损伤条件下两组巨噬细胞表型的差异。MSCs干预方法为加入MSCs上清0.5 ml,培养48 h。结果在各非干预组中,与正常条件下相比,各损伤条件下的M1型巨噬细胞比例、M1/M2值和IL-6水平均显著增高,而M2型巨噬细胞比例以及IL-10和PGE2水平均显著降低。MSCs干预后,在LPS和高糖+LPS的损伤条件下,与非干预组相比,干预组的M1型巨噬细胞的比例和M1/M2值均显著降低,而M2型巨噬细胞的比例均增加,ELISA结果也显示,在各损伤条件下,与非干预组相比,干预组的IL-6水平均显著降低,而IL-10和PGE2的水平均显著增加。结论高糖及慢性炎症因素叠加可加剧巨噬细胞向M1促炎表型极化及炎症因子的分泌,MSCs上清作用于损伤的巨噬细胞,促使其向M2抗炎表型极化,同时使炎症因子分泌减少,抗炎因子分泌增多。     

肝巨噬细胞在肝胰岛素抵抗发生中的作用

肝脏作为主要代谢器官,在维持机体糖脂代谢稳态中起重要作用。肝巨噬细胞激活可导致肝脏炎症反应,轻度慢性组织炎症是IR的关键因素。肝巨噬细胞分泌的炎症因子、巨噬细胞促炎型/抑炎型极化及其表面受体均参与调控糖脂代谢,在IR发生发展中发挥重要作用。药物、微量营养素、肝巨噬细胞受体识别、运动训练等通过影响肝巨噬细胞以改善IR,提示肝巨噬细胞可能是治疗IR及代谢性疾病的新靶点,为临床防治代谢性疾病提供新思路。     

E-巨噬细胞极化在心肌梗死后炎症反应中的研究进展

正急性心肌梗死(AMI)是全球主要的死亡和残疾原因之一。心肌梗死(心梗)引起的过度促炎反应是加剧心肌损伤和功能障碍的主要原因,因此抗炎治疗可能作为一种新的方法以缩小心梗范围,防止进一步的心脏重构和进展为心力衰竭~([1])。然而,许多抗炎干预措施在临床试验中效果不佳[2])。因此,了解控制心脏炎症的新机制对于确定治疗缺血性心脏病的新的靶点至关重要。免疫系统的激活与心梗后的炎症反应密切相关。其中机体固有免疫细胞巨噬细胞在心梗后炎症反应过程中发挥着重要作用。不同微环境下,巨噬细胞由于自身很强的功能可塑性,可极化成两种具有不同免疫功能的活化模式:经典型(M1型)和修复型(M2型)。它们分别通过分泌促炎和抗炎因子,参与心室重构的全过程。二者功能相反却又互相转化~([3])。因此在MI后由M1向M2表型转化是减少MI后不良左室重构从而改善心功能的关键。本文将巨噬细胞极化在心梗后炎症反应中的作用特点及其分子机制作一综述。     

巨噬细胞在蠕虫感染中的免疫功能

早在20多年前就有人认识到巨噬细胞(Mφ)对肿瘤细胞的细胞毒作用,但Mφ在蠕虫感染中的免疫功能直到最近才引起人们的重视。由于蠕虫(例如血吸虫、丝虫和钩虫等)是危害人体的主要寄生虫,因此,了解机体对蠕虫感染的免疫防御机制具有实际的临床意义。通过一系列的实验研究表明,Mφ在抗蠕虫感染时具有明显的免疫效应。一般认为Mφ对多细胞的寄生虫可通过多种途径产生细胞毒作用:包括自然杀伤活动和在补体     

大麻素CB2受体通过调节大鼠库普弗细胞极化防治酒精性肝病

【据Hepatology2011年10月报道】题:大麻素CB2受体通过调节大鼠库普弗细胞极化防治酒精性肝病(作者Louvet A等)巨噬细胞的激活有多种形式,主要是经典激活途径(classicalactibated macrophage,M1型)以及替代激活途径(alternative actibated macrophage,M2型)。M1型的激活主要     

姜黄素对不同亚型THP-1来源巨噬细胞表达炎症因子的抑制作用

目的 探讨姜黄素对M0、M1和M23种亚型巨噬细胞表达炎症因子的影响。方法 构建M0型/M1型/M2型巨噬细胞模型以及不同浓度梯度的姜黄素干预组和对照组，通过实时荧光定量PCR及酶联免疫吸附方法分别测定不同分组中TNFα、IL-6以及IL-123种炎症因子的表达。结果 实时荧光定量PCR结果显示，与对照组相比，姜黄素对3种亚型巨噬细胞TNFα、IL-6以及IL-12 mRNA的表达均具有明显抑制作用(P<0.01)，酶联免疫吸附实验也证实姜黄素能抑制以上3种细胞炎症因子的分泌水平(P<0.01)。结论 姜黄素对M0、M1和M23种亚型的巨噬细胞炎症因子表达水平均有不同程度的抑制作用，且呈剂量依赖关系。     

关注巨噬细胞在慢性低度炎症性疾病中的作用

已知巨噬细胞在先天免疫系统中发挥着重要的防御作用.近年来,随着慢性低度炎症性疾病概念的提出及深入研究,有关巨噬细胞活化平衡及其在慢性低度炎症性疾病,如肥胖、2型糖尿病、动脉粥样硬化和非酒精性脂肪性肝病等疾病中的致炎作用也逐渐成为当前研究的热点.本文主要阐述了巨噬细胞在这类疾病发生及发展中的重要作用.

Abstract：

It is well known that the macrophages play an important defensive role in the innate immune system. During recent years, with the introduction of the concept of chronic low-grade inflammatory diseases and their further intensive study, the activation and balance of macrophage, as well as its inflammatory effects in chronic lowgrade inflammatory diseases, such as obesity, type 2 diabetes, atherosclerosis, and non-alcoholic fatty liver, are gradually becoming a hot topic of current research. The present article mainly gives an overview of the important role played by macrophages in the inflammatory effects in these diseases.     

Advances in understanding the pathogenesis of HLH

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X‐linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule‐dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi‐organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined.     

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.     

Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages

Obesity is frequently associated with an infiltration of macrophages into adipose tissue. Adipocyte dysfunction causes a phenotypic switch of macrophages from an alternatively activated M2-like phenotype towards a proinflammatory M1 phenotype. The cross talk between adipocytes and infiltrating immune cells, in particular macrophages, is thought to contribute to local and eventually systemic inflammation. Here, we tested the phenotypic impact of a lack of adipocytes on the inflammatory status of macrophages. We took advantage of the fat apoptosis through targeted activation of caspase-8 (FAT-ATTAC) mouse model that allows for the inducible system-wide elimination of adipocytes through a proapoptotic mechanism and followed the degree and type of inflammatory response upon ablation of live adipocytes. Analysis of depots 2 wk after elimination of adipocytes resulted in markedly reduced levels of adipose tissue and a robust down-regulation of circulating adipokines. Quantitative PCR and immunohistochemistry on epididymal and inguinal fat depots revealed an increase of the macrophage markers F4/80 and CD11c. Using polychromatic flow cytometry, we observed an up-regulation of alternatively activated M2 macrophage markers (CD206 and CD301) on the majority of F4/80 positive cells. Apoptosis of adipocytes is sufficient to initiate a large influx of macrophages into the remnant fat pads. However, these macrophages are alternatively activated, antiinflammatory M2 macrophages and not M1 cells. We conclude that adipocyte death is sufficient to initiate macrophage infiltration, and live adipocytes are required to initiate and/or sustain a proinflammatory response within the infiltrating macrophages in adipose tissue.     

Cytokines and gastrointestinal disease mechanisms

Cytokines mediate immune responses and are detectable in the normal gastrointestinal mucosa. It is unclear how cytokines are physiologically regulated but in inflammatory enteropathies their expression is often greatly increased and may account for the tissue damage observed.T-cells may be sub-divided according to the pattern of cytokines which they secrete. TH1 cytokine expression is increased in delayed type IV cell mediated immune responses whereas TH2 cytokines are raised in diseases in which humoral mechanisms are more important. Cytokines are secreted by macrophages in relatively greater amounts than from T-cells. They are non-specific products of inflammation and may account for the majority of tissue damage seen in mucosal disease. The pattern of cytokine secretion may determine the immunopathogenesis of an inflammatory disorder.The ultimate goal of cytokine research is the development of therapeutic measures based on a better understanding of their actions which may be achieved with a better understanding of the molecular immune-microenvironment in inflammatory enteropathies. Studies with transgenic mice and gene targeted mice have important implications to the understanding of the immune system and its role in intestinal diseases.     

PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells

PD-L1 and PD-L2 are ligands for PD-1, a costimulatory molecule that plays an inhibitory role in regulating T cell activation in the periphery. We find that PD-L1 is highly expressed on inflammatory macrophages as compared with resident peritoneal macrophages but can be induced on resident macrophages by classical activation stimuli such as lipopolysaccharide, IFN-gamma, and polyinosinic-polycytidylic acid. Further up-regulation of PD-L1 on inflammatory macrophages can also be induced by subsequent exposure to lipopolysaccharide and IFN-gamma. In contrast, PD-L2 is not expressed on inflammatory macrophages but can be induced by alternative activation via IL-4. Although PD-L1 is highly inducible on a variety of antigen-presenting cell lines as well as resident macrophages, PD-L2 is most significantly inducible only on inflammatory macrophages. PD-L1 up-regulation depends on TLR4 and STAT1, whereas PD-L2 expression depends on IL-4R alpha and STAT6. Consistent with these results, T helper 1T helper 2 (Th1/Th2) cells also differentially up-regulate PD-L1 and PD-L2 expression on inflammatory macrophages. Hence, Th1 cells as well as microbial products can enhance PD-L1 expression on many different macrophage populations, whereas Th2 cells instruct only inflammatory macrophages to up-regulate PD-L2. These results suggest that PD-L1 and PD-L2 might have different functions in regulating type 1 and type 2 responses.