中性粒细胞胞外诱捕网在病毒性心肌炎中的作用

病毒性心肌炎(VMC)是临床常见的心血管疾病,炎症免疫应答是VMC的主要发病病因。中性粒细胞作为先天免疫应答的一部分在VMC中发挥的作用过去很少被研究。然而多个研究表明,中性粒细胞可通过一种新的防御机制即中性粒细胞胞外诱捕网(NETs)的形成参与多种疾病。并且,最近在活动性心肌炎患者和VMC模型心肌病理活检中都发现有NETs形成,因此NETs被推测在VMC发病过程中发挥一定作用。本文就NETs在VMC中的作用作一综述。     

中性粒细胞胞外诱捕网在胃肠道中的应用

中性粒细胞胞外诱捕网(neutrophil extracellulartraps,NETs)在感染过程中具有重要作用,它可以帮助中性粒细胞捕获和杀死病原体。然而,越来越多的证据表明,不受控制或过量的NETs与炎症的加剧和自身免疫的发展、癌症转移以及不适当的血栓形成有关。并进一步阐述NETs在胃肠系统中的作用,概述它们的保护机制和病理作用,讨论NETs形成的最新机制,微生物和NETs之间的相互作用以及中性粒细胞亚型与它们功能之间的关系。此外,NETs相关分子,包括游离DNA和超瓜氨酸化组蛋白等,可作为生物标志物和胃肠道疾病治疗干预的靶点。     

中性粒细胞胞外诱捕网在抗寄生虫免疫中的作用研究进展

中性粒细胞胞外诱捕网（neutrophil extracellular traps, NETs）是活化的炎性中性粒细胞在感染或炎症应答期主动释放的一种串珠样纤维网状物质,由染色质DNA和多种胞内蛋白成分组成,可通过缠绕致病菌限制其扩散,同时通过各种抗菌蛋白杀伤致病菌,被认为是中性粒细胞除吞噬和脱颗粒作用外的第三种杀菌机制。近年研究显示,NETs也参与抗寄生虫免疫过程。本文就NETs在抗寄生虫免疫中作用的研究进展作一综述,以期为寄生虫病发病机制研究以及相关治疗药物开发提供参考。     

中性粒细胞胞外陷阱在肾脏疾病中的研究进展

中性粒细胞胞外陷阱(NETs)是一种由染色质和多种颗粒蛋白组成的细胞外网状结构。形成NETs是中性粒细胞的一种新型死亡方式, 亦是一种新型作用机制。研究表明, NETs能杀灭多种病原体。然而, NETs亦通过不同的作用参与多种疾病的发生发展, 肾脏是NETs主要累及的器官之一。本文就NETs 的形成及其在多种肾脏疾病中的研究进展进行综述, 为肾脏疾病的治疗提供新思路。     

中性粒细胞胞外诱捕网的作用机制及其在多种疾病中作用的研究进展

中性粒细胞胞外诱捕网(NETs)是中性粒细胞发挥生物学作用的另一种表现形式。除了具有强大的抗感染作用以外,它亦对机体产生直接或者间接的损伤,可与炎症因子相比拟。近年来研究表明NETs在抗炎、血栓形成、自身抗体的产生等方面均有参与。本文就NETs的基本组成结构以及在多种疾病发生、发展中的作用作一综述。     

中性粒细胞胞外诱捕网在痛风中的研究现状与进展

痛风是嘌呤生成和代谢异常导致单钠尿酸盐(MSU)结晶沉积在关节及周围组织引发的一组异质性疾病。中性粒细胞胞外诱捕网(NETs)作为机体受到刺激时对抗细胞外病原体的免疫策略之一, MSU晶体诱导的NETs可激发促炎反应, 而聚集的NETs(aggNETs)可以通过降解促炎细胞因子和趋化因子进而缓解急性痛风性炎症, 并且NETs可以与MSU晶体结合共同参与痛风石的形成。本文概述了痛风中NETs形成的机制及在痛风不同阶段NETs发挥的作用, 以期为痛风的诊治找到新的靶点。     

NETs与心血管疾病的相关研究

中性粒细胞胞外诱捕网(NETs)是活化的中性粒细胞所释放的去聚化染色质DNA和多种抗菌蛋白所组成的纤维网状复合物。NETs可参与机体免疫应答限制病原菌，并导致组织及器官损伤，现有研究发现NETs可参与到动静脉的血栓形成。本文对NETs的结构、发生机制、重要成分及在动脉粥样硬化及血栓中的作用进行综述。     

中性粒细胞胞外捕网、血小板和肿瘤的关系

血小板除了在止血中发挥重要作用以外,还会参与炎症的发生和肿瘤的进展等病理生理过程。肿瘤微环境中促凝血因子的异常表达或暴露可诱导血小板活化,进而导致血小板释放生长因子。由于肿瘤诱导的血小板活化,癌症患者通常会出现不同程度的静脉血栓。而中性粒细胞胞外捕网(NETs)的形成可能是导致癌症相关血栓形成的新因素。细胞核或线粒体来源的DNA外显化之后,与组蛋白和颗粒蛋白酶[如中性粒细胞弹性蛋白酶(NE)和过氧化物酶(MPO)]结合形成NETs。NETs有助于中性粒细胞捕获和杀死病原体,如细菌、病毒和真菌。本文将重点介绍在感染和无菌条件下,我们目前对血小板作为NETs形成调节因子作用的认识。     

中性粒细胞胞外诱捕网和斑块血栓形成关系研究的新进展

中性粒细胞胞外诱捕网(NETs)能够捕获并抑制病原微生物扩散,杀灭并清除病原体,同时也参与自身免疫性疾病的发生和进展。这种中性粒细胞的不同于趋化、吞噬的杀菌方式成为了近年来的研究热点。NETs不仅仅出现在血栓和斑块中,而且可能在引发动脉粥样硬化斑块形成和动脉血栓形成中发挥重要的作用。本文就NETs促进动脉粥样硬化斑块及血栓形成的研究进展作一综述。     

肽酰基精氨酸脱亚氨酶4和中性粒细胞胞外诱捕网形成在实验性动脉粥样硬化和动脉损伤中的作用:浅表糜烂的影响

正中性粒细胞可能促进人类动脉粥样硬化的血栓并发症的发生。特别是中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)可加剧局部炎症,并放大和加剧动脉内膜损伤和血栓形成。肽酰基精氨酸脱亚氨酶4(peptidyl arginine deiminase 4,PAD4)参与NET的形成,但对该酶在动脉粥样硬化血栓形成中的     

T cells in systemic sclerosis: a reappraisal

SSc is an autoimmune disease characterized by inflammation and extracellular matrix deposition that ultimately leads to loss of organ function. T cells appear to play a prominent role in its pathogenesis. The evidence for this comes from their being at the site of fibrosis, their activated phenotype and alteration in their number and frequency in peripheral blood. This review examines the role of T cells in the pathogenesis of SSc and specifically examines the key soluble profibrotic mediators (IL-4, IL-6, IL-13) secreted by Th2 cells and their interactions with fibroblasts that deposit excess extracellular matrix leading to fibrosis. We finally examine possible therapeutic options in targeting T-cell mediators to disrupt the cellular interactions between T cells and fibroblasts that serve to drive the fibrotic response. One of the factors driving fibrosis is IL-6 and this can be neutralized in vivo not only to limit IL-6-driven tissue fibrosis but concomitantly to suppress switching of Tregs to Th17 T cells that will provide more IL-6, thus perpetuating the fibrosis. Taken together, these data implicate the role of T cells in SSc and suggest that Th2-polarized T cells and the fibrotic mediators subsequently released directly induce fibrosis. Targeting such cytokines may be therapeutic not only in SSc but more generally in diseases where fibrosis is directed by inflammatory signals.     

A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

IgG4-related disease (IgG4RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4RD may be present in a certain proportion of patients with a wide variety of diseases, including Mikulicz's disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor. Although IgG4RD forms a distinct, clinically independent disease category and is attracting strong attention as a new clinical entity, many questions and problems still remain to be elucidated, including its pathogenesis, the establishment of diagnostic criteria, and the role of IgG4. Here we describe the concept of IgG4RD and up-to-date information on this emerging disease entity.     

IgG4‐related disease

Immunoglobulin G4‐related disease (IgG4‐RD) is a regional or systemic fibro‐inflammatory disease of unknown etiology. It presents a distinctive histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4‐positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or tumefactive lesions. This new disease entity includes a wide variety of diseases such as Mikulicz disease, autoimmune pancreatitis, Riedel thyroiditis, interstitial nephritis and retroperitoneal fibrosis. Glucocorticoid therapy can resolve the clinical and pathological abnormalities and impaired organ function. IgG4‐RD was recognized internationally in 2011, and new evidence has accumulated regarding its pathogenesis, clinical features and treatment. In this review, we outline our present understanding of IgG4‐RD.     

Redox-active protein thioredoxin prevents proinflammatory cytokine- or bleomycin-induced lung injury

Thioredoxin (TRX) is a multifunctional redox (reduction/oxidation)-active protein that scavenges reactive oxygen species by itself or together with TRX-dependent peroxiredoxin. TRX also has chemotaxis-modulating functions and suppresses leukocyte infiltration into sites of inflammation. Leukocyte infiltration and oxidative stress may be involved in the pathogenesis of several diseases, including interstitial lung diseases (ILD). We examined the effects of TRX in two mouse models of human ILD. Recently, we established a new mouse model for human ILD in which daily administration of proinflammatory cytokine interleukin (IL)-18 with IL-2 induces lethal lung injury accompanied by acute interstitial inflammatory responses. Administration of recombinant TRX suppressed IL-18/IL-2-induced interstitial infiltration of cells and prevented death and lung tissue damage. TRX-transgenic mice also showed resistance to lethal lung injury caused by IL-18/IL-2. Administration of bleomycin induces the infiltration of polymorphonuclear and mononuclear leukocytes in the pulmonary interstitium, followed by progressive fibrosis. Wild-type mice given recombinant TRX treatment and TRX-transgenic mice demonstrated a decrease in bleomycin-induced cellular infiltrates and fibrotic changes in the lung tissue. These results suggest that TRX modulates pulmonary inflammatory responses and acts to prevent lung injury. TRX may have clinical benefits in human ILD, including lung fibrosis, for which no effective therapeutic strategy currently exists.     

Mast cells in allergy and host defense.

Mast cells have been implicated in the pathogenesis of allergic diseases and in inflammatory responses associated with pathological immune and disease-related processes including fibrosis, autoimmune pathology, and neoplasia. Recent findings in animal models of bacterial infection also suggest that mast cells may have a protective role in host defense against pathogens in innate immunity along with the probable role of mast cells in acquired immunity against parasitic infections. Mast cells are strategically located at the host-environment interface and may provide an early defense against an invading pathogen. Mast cells express an array of adhesion and immune receptors that may assist in the recognition of invading pathogens. When activated, these cells then synthesize and release key immunoregulatory cytokines, one consequence of which is to mobilize a rapid and vigorous inflammatory response. However, although it has been demonstrated that mast cells may have a role in innate immunity in defined in vitro and animal models, it remains to be determined whether mast cells are protective in innate immune responses in humans.     

Pathogenic helper T cells

Intractable chronic inflammatory diseases, including autoimmune diseases, autoinflammatory diseases and allergic diseases, are caused by disruption or failure of the immune system. Pathogenic immune cells are presumed to be closely related to the pathogenesis of intractable diseases, but the precise cellular and molecular mechanisms underlying the pathogenesis of these diseases remain unclear. The balance between the T helper type 1 (Th1) and Th2 cell fractions has been believed to be responsible for the differences among inflammatory diseases. However, an analysis of the cells infiltrating inflammatory lesions in mice and humans revealed the generation of pathogenic Th cells with different characteristics at the memory T-cell stage in the peripheral tissues in various inflammatory diseases. In this review, we will summarize and discuss recent progress regarding the characteristics of pathogenic Th cells, their mode of action, and the molecular mechanisms that regulate the pathology of intractable chronic inflammatory diseases, particularly those with tissue fibrosis. We hope this article will help clarify the pathogenesis of these diseases and propose a future direction for research.     

The role of inflammation, humoral and cell mediated autoimmunity in the pathogenesis of atherosclerosis

The pathogenesis of atherosclerosis has not been well defined and many questions remain unanswered. Many studies have discussed the importance of inflammation as the first step in promoting endothelial dysfunction and atherosclerosis.The association of inflammatory markers such as fibrinogen and C reactive protein (CRP) with atherosclerosis and cardiovascular/cerebrovascular clinical events reinforces the pivotal role that inflammation plays in the atherosclerotic process.The humoral and cellular autoimmune response against antigens expressed in the endothelium and the greater prevalence of atherosclerosis in immune-mediated rheumatic diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) strongly suggest the involvement of autoimmunity in the atherosclerotic process. The role of inflammation and autoimmune responses in atherosclerosis are discussed in order to better understand their close link on its pathogenesis.     

细胞因子对肺纤维化的影响及其作用机制研究进展

肺纤维化是不同病因所致各种肺间质疾病的共同结局,近年其发病率及病死率呈增高趋势,目前国内外多数学者认为,炎症细胞及其释放的多种细胞因子在肺纤维化的发病机制中起着中心环节的作用.本文对目前肺纤维化相关细胞因子及其作用机制研究进展作一简要概述.     

Th17/Treg失衡与炎症性肠病的关系

炎症性肠病(inflammatory bowel disease.IBD)的病因和发病机制尚未完全明确,肠道黏膜免疫系统异常反应所导致的炎症过程在发病中起重要作用.辅助性T细胞17(T helper 17 cells,Th17)可介导慢性炎症和自身免疫性疾病的发生,调节性T细胞(regulatory T cell,Treg)有抑制自身免疫的功能,二者存在相互转化的关系.有研究表明Th17/Treg转化平衡是维持肠道免疫稳态的重要因素,这可能是导致人类IBD的原因之一.最近研究表明TGF-β,IL-6和维甲酸(retinoic acid,RA)可能是调控二者平衡关系的重要因素.肠道菌群(intestinal flora)与IBD的发生发展关系密切,益生菌(probiotics)对IBD的治疗作用成为研究的热点.深化对Th17/Treg转化调控关系的研究是当前重要的研究课题.