活性氧调控巨噬细胞极化的研究进展

巨噬细胞可以极化为两种表型:经典激活巨噬细胞(M1)和替代激活巨噬细胞(M2),前者分泌促炎细胞因子来促进炎性反应,而后者分泌炎性抑制因子抑制过量炎性反应、促进血管生成、组织修复和肿瘤生长等。作为重要的第二信使,活性氧(ROS)不仅导致促炎细胞因子的产生,而且促进肿瘤的发生和发展。在不同刺激条件下,ROS可调控巨噬细胞的极化过程,使其向不同表型转换,从而发挥不同作用。     

巨噬细胞的极化及功能调控

巨噬细胞在体内分布极广,具有高度可塑性,并在机体的发育及内环境的平衡中起到重要作用。应激条件下,巨噬细胞发生极化,极化后的巨噬细胞亚型可以细致调节及回应各种不同的刺激,对炎症反应或疾病的发展及组织器官的修复程度起着关键性的作用,具有重要的临床应用价值。我们在文中概述了巨噬细胞的极化分类,作用机制及不同环境下巨噬细胞的功能转换,为巨噬细胞极化研究提供理论基础。     

巨噬细胞极化信号通路及其调控机制研究进展

巨噬细胞是一类具有异质性和可塑性的免疫细胞,由单核细胞分化而来,在不同环境下可极化为不同的表型,分化中的巨噬细胞可位于极端分化的两型中的任意阶段。巨噬细胞在此极化过程中涉及较多的信号通路和转录调控,故本文将介绍具体巨噬细胞极化的通路及调控因子。     

病原菌影响巨噬细胞极化的研究进展

巨噬细胞作为固有免疫系统中的重要一员,具有吞噬、抗原呈递、杀伤病原体等功能,在早期控制病原菌感染中发挥重要作用。病原菌可诱导巨噬细胞发生M1/M2型极化而参与机体对病原菌感染的免疫应答。病原菌运用不同的策略诱导巨噬细胞极化,对感染性疾病转归产生重要的影响。     

代谢产物通过表观遗传机制调控巨噬细胞极化的研究进展

巨噬细胞是参与固有免疫和适应性免疫的重要细胞,在抵抗病原体、促进组织发育、维持稳态和修复损伤中有着重要作用。近来研究发现,某些代谢产物可调节表观遗传酶的活性,从而通过表观遗传机制调控巨噬细胞的极化,影响相关疾病的发生发展。为此本文就代谢产物通过表观遗传机制调控巨噬细胞极化的相关研究进展作一综述。     

代谢性疾病中巨噬细胞极化的机制及运动对其调控作用的研究进展

本文综述了运动对代谢性疾病中巨噬细胞极化的影响及其发挥作用的可能机制。近年来,巨噬细胞极化以其在代谢性疾病中的重要调控作用而在运动科学研究领域备受关注。随着研究的深入,发现不同方式运动均可通过增加巨噬细胞M2型极化产生抗炎效应以改善机体代谢,促进健康。因此,运动作为防治代谢性疾病的有效手段,其促进健康的机制可能与促进巨噬细胞M2型极化有关。可能的调控机制如下：(1)运动通过抑制TLR4活性、下调NF-κB信号下调TLR通路,减少巨噬细胞M1型极化;(2)运动通过改善肥胖下调JNK通路,抑制巨噬细胞M1型极化;(3)运动通过增加机体IL-13和IL-4分泌促进AMPK磷酸化、PPAR激活、SCOS1表达并抑制SCOS3表达激活AMPK通路、JAK/STAT通路和PI3K/AKT通路以促进巨噬细胞M2型极化。综上,运动可通过调节多条信号通路发挥促进巨噬细胞M2型极化并抑制M1型极化作用,这可能是运动改善机体代谢以促进健康的途径之一。     

巨噬细胞极化与细胞代谢的相互调控

巨噬细胞极化对于机体抵抗病原微生物感染及组织修复等过程中发挥着重要作用。γ干扰素(IFN-γ)和脂多糖(LPS)活化的巨噬细胞称之为经典活化的巨噬细胞(M1),而白细胞介素4(IL-4)和IL-13诱导巨噬细胞的替代激活(M2)。巨噬细胞的极化受到细胞代谢调控,M1型巨噬细胞主要为糖酵解、戊糖磷酸代谢途径供能,而M2型巨噬细胞主要为氧化磷酸化途径参与。本文在总结了巨噬细胞极化对细胞代谢影响的基础上,重点探讨了糖、脂、氨基酸、铁离子、氧化还原反应等代谢通路对其巨噬细胞表型和功能的调节作用。     

乳酸菌介导巨噬细胞极化作用的研究进展

乳酸菌可以在肠道内定植,维持肠道菌群平衡,通过产生有机酸、细菌素等抗菌物质抑制肠道内有害菌的生长。大量研究表明乳酸菌发挥益生作用的主要机制可能与它的活化和维持机体免疫屏障机制及调节肠道生理屏障功能密切相关。乳酸菌作为益生菌与免疫细胞之间有着不可分割的关系,尤其是巨噬细胞。它通过各种途径与巨噬细胞作用,使巨噬细胞产生细胞因子,并向不同的表型极化,参与模式识别受体包括Toll样受体(TLRs)、Notch、核因子κB(NF-κB)信号通路等,从而降低机体的炎症反应。在这过程中,乳酸菌在机体调节中发挥重要作用。本文主要对乳酸菌介导巨噬细胞产生免疫调节的作用机制进行阐述。     

YAP调控LPS诱导的巨噬细胞M1型极化

目的 探讨YAP对脂多糖(Lipopolysaccharide, LPS)诱导的巨噬细胞M1型极化的影响。方法 LPS诱导THP-1和U937细胞来源的M0型巨噬细胞向M1型极化。RT-qPCR法检测M1型巨噬细胞的标志物,罗丹明-鬼笔环肽检测细胞骨架,Western blot、RT-qPCR检测Hippo通路相关蛋白及其靶基因的表达。降低M0型巨噬细胞内YAP的表达,RT-qPCR检测LPS再诱导的M1型巨噬细胞的标志物的表达变化。结果 在M0型巨噬细胞向M1型极化过中,Hippo通路关键因子YAP的蛋白水平升高,下游靶基因的表达也升高;敲低YAP或使用维替泊芬抑制YAP表达后,LPS再诱导的M1型巨噬细胞标志物的表达明显降低。结论 YAP可以调控LPS诱导的巨噬细胞向M1极化。     

巨噬细胞的极化及其调控的信号分子和转录因子

巨噬细胞作为机体重要的免疫细胞,在炎症反应中具有重要的调节作用.研究表明,巨噬细胞具有较强的可塑性和异质性,在体内外不同微环境的影响下,尤其是在炎症反应过程中可分化成具有不同功能的表型即极化.由于巨噬细胞的极化和分型与炎症相关性疾病的发生发展有着密切关系,因此相关研究已成为近年来研究的热点.本文就相关领域的最新研究进展进行综述.     

Schistosoma japonicum infection induces macrophage polarization

The role of macrophages （MФ） as the first line of host defense is well accepted. These cells play a central role in orchestrating crucial functions during schistosomal infection. Thus, understanding the functional diversity of these cells in the process of infection as well as the mechanisms underlying these events is crucial for developing disease control strategies. In this study, we adopted a Mqb polarization recognition system. M1 macrophage was characterized by expressing CD16/32, IL-12 and iNOS. M2 macrophage was characterized by expressing CD206, IL-10 and arg-1. In vivo （mouse peritoneal macrophages of different infection stages were obtained） and in vitro （different S. japonicum antigens were used to stimulate RAW264.7） were characterized by using the above mentioned system. NCA and ACA stimulated RAW264.7 express significantly higher levels of IL-12 while significantly higher levels of IL-10 were detected after soluble egg antigen （SEA） stimulation. The results showed that dramatic changes of antigen in the microenvironment before and after egg production led to macrophage polarization. Furthermore, through TLR blocking experiments, the TLR4 signaling pathway was found to play a role in the process of macrophage polarization toward M1. Our data suggest that macrophage polarization during S. japonicum infection had significant effects on host immune responses to S. japonicum.     

B cells and Autoimmunity 2013

The beginning stages of liver damage induced by various etiologies (i.e. high fat diet, alcohol consumption, toxin exposure) are characterized by abnormal accumulation of lipid in liver. Alterations in intracellular lipid transport, storage, and metabolism accompanied by cellular insult within the liver play an important role in the pathogenesis of liver disease, often involving a sustained inflammatory response. The intracellular lipid transporter, fatty acid binding protein 5 (FABP₅), is highly expressed in macrophages and may play an important role in the hepatic inflammatory response after endotoxin exposure in mice. This study tested the hypothesis that FABP₅ regulates macrophage response to LPS in male C57bl/6 (wild type) and FABP₅ knockout mice, both in vitro and in vivo. Treatment with LPS revealed that loss of FABP₅ enhances the number of hepatic F4/80⁺ macrophages in the liver despite limited liver injury. Conversely, FABP₅ knock out mice display higher mRNA levels of anti-inflammatory cytokines IL-10, arginase, YM-1, and Fizz-1 in liver compared to wild type mice. Bone marrow derived macrophages stimulated with inflammatory (LPS and IFN-γ) or anti-inflammatory (IL-4) mediators also showed significantly higher expression of anti-inflammatory/regulatory factors. These findings reveal a regulatory role of FABP₅ in the acute inflammatory response to LPS-induced liver injury, which is consistent with the principle finding that FABP₅ is a regulator of macrophage phenotype. Specifically, these findings demonstrate that loss of FABP₅ promotes a more anti-inflammatory response.     

损伤周围神经的微环境中巨噬细胞极化成M2表型可有效促进其再生

背景：周围神经是人体最脆弱的结构,很容易因创伤而受损,巨噬细胞作为周围神经中最主要的免疫细胞,在周围神经损伤修复再生中发挥了极为重要的作用。随着对巨噬细胞各亚型功能及诱导机制研究越来越清楚,可以通过分子生物学方法诱导巨噬细胞成相应修复表型,并期许其成为周围神经损伤新的治疗靶点。目的：总结周围神经系统中巨噬细胞的起源、分类、巨噬细胞极化、极化调控以及在周围神经损伤修复再生中的应用。方法：通过检索CNKI、万方数据库、PubMed及Web of Science数据库相关文章。以“巨噬细胞极化,神经”为中文检索词,以“macrophage polarization,nerve”为英文检索词。然后根据纳入与排除标准对文章进行初筛,保留相关性和参考价值较高的73篇文章进行综述。结果与结论：巨噬细胞极化在周围神经损伤后的修复中发挥重要作用,有望成为治疗周围神经损伤的治疗靶点,但是控制这一过程的机制仍需要进一步深入研究,促进巨噬细胞M2极化的最佳方法也存在不确定性。因此,需要进一步研究巨噬细胞向M2极化的调控机制以及M2巨噬细胞如何调节神经功能恢复,为周围神经损伤的治疗奠定基础。https://orcid.org/0000-0003-0655-2810 (胡涛涛) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

A case in which biventricular assist device support was required after aortic valve replacement with a bioprosthetic valve

We report the case of a 45-year-old man with severe aortic regurgitation. The patient underwent aortic valve replacement with a bioprosthetic valve, but was unable to be weaned from cardiopulmonary bypass (CPB). Intraoperative coronary angiography revealed stenosis of the right coronary orifice, so an intra-aortic balloon pump was inserted and coronary artery bypass grafting to the right coronary artery was conducted; however, weaning from CPB again failed. Left ventricular assist using a Gyro centrifugal pump was performed between the left atrium and left femoral artery, along with right ventricular assist using a Nikkiso centrifugal pump between the right atrium and pulmonary artery. Flow rates averaged from 2.0 to 2.8l/min for the left-side ventricular assist device (VAD) and 2.1–3.8l/min for the right-side VAD. The bypass rate reached approximately 70% at maximum. No thromboembolic events were documented during VAD support. The patient underwent explantation of VADs on postoperative day 4. No thrombus was identified on the bioprosthetic aortic valve by transesophageal echocardiography. The left-side pump displayed no thrombus, while the right-side pump had a small thrombus at the shaft. The patient was discharged from the hospital and was alive as of 2 year postoperatively. To the best of our knowledge, no clinical study has yet compared the antithrombotic properties of two centrifugal pumps in one patient where mechanical support was performed for the same duration and flow rate.     

Response gene to complement 32 (RGC-32) expression on M2-polarized and tumor-associated macrophages is M-CSF-dependent and enhanced by tumor-derived IL-4

Response gene to complement 32 (RGC-32) is a cell cycle regulator involved in the proliferation, differentiation and migration of cells and has also been implicated in angiogenesis. Here we show that RGC-32 expression in macrophages is induced by IL-4 and reduced by LPS, indicating a link between RGC-32 expression and M2 polarization. We demonstrated that the increased expression of RGC-32 is characteristic of alternatively activated macrophages, in which this protein suppresses the production of pro-inflammatory cytokine IL-6 and promotes the production of the anti-inflammatory mediator TGF-β. Consistent with in vitro data, tumor-associated macrophages (TAMs) express high levels of RGC-32, and this expression is induced by tumor-derived ascitic fluid in an M-CSF- and/or IL-4-dependent manner. Collectively, these results establish RGC-32 as a marker for M2 macrophage polarization and indicate that this protein is a potential target for cancer immunotherapy, targeting tumor-associated macrophages.     

A new method of eliciting delayed hypersensitivity in the mouse abdominal cavity

A new method of determining delayed hypersensitivity quantitatively was investigated in mice. Mice were sensitized with 150 micrograms of ferritin and, 3 weeks later, antigen challenge was performed by implanting a sponge containing antigen in the abdominal cavity. Cells accumulated in the sponge markedly increased in number for 24-72 h after the challenge; mononuclear cells predominated by 48 h. When sensitized lymphocytes were transferred passively to a normal recipient, marked cell accumulation in the sponge was found 48 h after the challenge. Immunological specificity was confirmed in animals sensitized to antigen and receiving passive transfer of sensitized cells. Strain differences in this reaction were observed. Cortisone (20 mg/kg for 6 days before challenge) significantly decreased cell accumulation. Delayed hypersensitivity was also elicited in the ear of sensitized animals. Extracts of sponges removed from antigen-challenged mice had macrophage chemotactic activity.