CXC趋化因子配体16及其受体与动脉粥样硬化的关系

CXC趋化因子配体16(CXCL16)是一种具有黏附分子、趋化因子、清道夫受体功能的趋化因子家族中的一员,可促进活化的T淋巴细胞与内皮细胞间的黏附,平滑肌细胞的增殖及抗原递呈细胞在炎症部位的聚集,增加巨噬细胞对氧化型低密度脂蛋白的摄取,促进泡沫细胞形成,并参与到动脉粥样硬化、血管狭窄、炎症反应的发生发展中。CXCL16及其受体与动脉粥样硬化、冠心病、脑卒中等血液循环系统疾病的发生、严重程度及预后相关,并在临床疾病发生预测中有一定作用。     

趋化因子CXCL16与动脉粥样硬化性脑血管病的研究进展

动脉粥样硬化（atherosclerosis,AS）是脑血管病的重要病因。在我国,随着生活水平的提高,AS性脑血管病的患病率和病死率迅速增长,严重威胁我国人民健康、影响生活质量。趋化因子CXCL16是在AS损伤部位新发现的一类跨膜趋化因子,具有趋化因子、黏附分子和清道夫受体等多种作用。很多研究表明,CXCL16与AS性脑血管病有着密切的关     

趋化因子及其受体与冠心病关系的研究进展

动脉粥样硬化(AS)是慢性炎性及代谢性疾病,脂质沉积和炎性细胞浸润至血管内皮下是形成AS的主要原因,但是炎性细胞浸润的机制尚未阐明。许多国内外研究表明,趋化因子对单核细胞、巨噬细胞、T细胞等炎性细胞的迁移、活化在AS炎症反应中起重要作用。新近研究证实,趋化因子可促使血管平滑肌细胞增殖以及炎症因子和基质金属蛋白酶的合成,促进斑块不稳定的关键环节。本文就趋化因子及其受体在AS发生发展中的作用予以综述。     

CXCL10与CXCR3在ARDS中的研究进展

CXC趋化因子配体10 (CXCL10)又称γ干扰素诱导蛋白10 (IP-10),属于CXC类非ELR亚族趋化因子之一,是γ干扰素诱导产生的可以趋化多种炎症细胞如T淋巴细胞,单核细胞和自然杀伤细胞的一类蛋白质.CXCL10通过与特异性CXC趋化因子受体3(CXCR3)结合调节炎症反应,促进ARDS的病理过程.本文旨在阐述CXCL10与CXCR3在ARDS中的作用,为ARDS的治疗提供新思路.     

趋化因子CXCL16与动脉粥样硬化的研究现状

近年新发现的跨膜趋化因子CXCL16既具有趋化因子的功能,可以趋化激活的T淋巴细胞,促进T细胞与抗原递呈细胞的作用,同时还可作为清道夫受体吞噬氧化型低密度脂蛋白,促进泡沫细胞形成,此外CXCL16还有促进平滑肌细胞、内皮细胞增殖,增加细胞与细胞黏附的作用,动脉粥样硬化斑块处巨噬细胞和平滑肌细胞CX-CL16表达增高,因此CXCL16可能在多个环节参与动脉粥样硬化的发生、发展。     

趋化因子CXCL10(IP-10)/CXCR3在类风湿关节炎发病中的作用及应用前景

类风湿关节炎（RA）是一类以关节炎为主要临床表现的系统性自身免疫性疾病。实验证明,T细胞尤其是CD4~＋T细胞的异常活化及其分泌的细胞因子所形成的网络参与了RA激发和延续。趋化因子在炎症细胞向滑膜组织迁移及活化过程中发挥了关键作用,趋化因子C-X-C配体10/干扰素诱导蛋白-10（CXCL10/IP-10）可与表达在T细胞表面的受体趋化因子C-X-C受体3（CXCR3）结合促进其活化并向CD4~＋Th1细胞方向分化,从而促进炎症反应。研究发现,CXCL10在RA血清及滑膜中表达增高。目前作为RA的一个可能的致病因素,CXCL10/CXCR3在发病机制中的作用越来越受到重视。研究发现,CXCL10抗体及裸DNA疫苗可对RA关节炎有抑制及治疗作用,其可能作为RA治疗新靶点的研究日益增多。     

CXCL16与肝脏疾病的研究进展

趋化因子是一类能够吸引免疫细胞到特定部位的细胞因子,在免疫调节和免疫病理反应中发挥重要作用。CXCL16是一个新发现的趋化因子,它是迄今第二个既能以分泌又可以膜结合形式存在的趋化因子,在肝脏的免疫反应体系中的作用越来越受到更多学者的关注,并且其将为肝脏疾病的治疗提供一个新的策略。本文就CXCL16与肝脏疾病的研究状况作一综述。     

趋化因子配体13在常见感染性病原体感染中的表达及意义

趋化因子配体13(C-X-Cmotifchemokineligand13,CXCL13)又称B细胞吸引趋化因子1或B淋巴细胞趋化因子,通过与B细胞、辅助T细胞上的G蛋白偶联趋化因子受体结合,诱导其向生发中心运输,促进B细胞成熟和抗体应答,从而实现对病毒清除以及炎症的快速控制。然而,目前相关研究表明CXCL13水平过高可能导致免疫反应受损,促进疾病进展。CXCL13水平变化可作为反映疾病进展、抗病毒疗效有效指标,并且对疫苗研发有所帮助。因此,本文主要对CXCL13在常见感染性病原体感染如人类免疫缺陷病毒感染、乙型肝炎病毒感染、结核分枝杆菌感染以及SARS-CoV-2感染中的表达及其意义进行综述。     

气道平滑肌细胞与黏附分子及趋化因子的相互作用

气道平滑肌在支气管哮喘(简称哮喘)发生过程中,具有调节气道炎症程度和收缩功能的作用,其与细胞黏附分子和趋化因子的相互作用可能是重要的调节因素.气道平滑肌细胞能表达某些细胞黏附分子及趋化因子,其中平滑肌细胞表面表达的胞间黏附分子1和血管细胞黏附分子1是介导平滑肌细胞与免疫细胞黏附最重要黏附分子;同时,平滑肌细胞可分泌嗜酸粒细胞趋化因子等多种炎症趋化因子诱导炎症细胞向气道壁定向移动并定植.这些黏附分子和趋化因子使平滑肌细胞与各种免疫细胞的相互作用,加重哮喘炎症反应.而通过抑制上述黏附分子和趋化因子的作用,则能够改善局部炎症反应,减轻气道痉挛.这一现象提示,改变气道平滑肌细胞的功能,减少其对黏附分子和趋化因子的合成与表达,可能成为减轻哮喘气道炎症反应,改善哮喘症状的新途径.     

CXCL16与动脉粥样硬化

趋化因子是一组具有趋化作用的细胞因子,能吸引免疫细胞到免疫应答局部,参与免疫调节和免疫病理反应.目前,已知的趋化因子可分为CC、CXC、C及CX3C 4个家族和诱导性及组成性两类.CXCL16是近年在人动脉粥样硬化损伤部位的巨噬细胞中发现的一种趋化因子,同时也是一种膜结合蛋白,起到清道夫受体的作用.它属于CXC家族,同时具有CC家族和CX3C家族（如：不规则趋化因子Fractalkine）趋化因子的特征,它包含跨膜区和黏蛋白样结构。我们从CXCL16的基本特征、病理生理功能尤其与动脉粥样硬化关系的研究现状和最新进展作一简要综述。     

Identification of chemokines important for leukocyte recruitment to the human endometrium at the times of embryo implantation and menstruation

Human endometrium possesses a unique immunological environment enabling implantation of the semiallogeneic embryo. Large populations of macrophages and uterine-specific natural killer cells infiltrate the implantation site, believed to be important modulators of trophoblast invasion and decidualization. In the absence of pregnancy, there is a dramatic influx of neutrophils, eosinophils, and macrophages, likely to be critical for focal inflammatory endometrial destruction. However, little is known regarding selective recruitment of leukocyte subtypes. We employed a gene array approach to analyze the expression of 21 chemokines in endometrium. Real-time RT-PCR and immunohistochemistry was conducted to verify expression patterns and determine cellular source. Nine chemokines were highly abundant in human endometrium: monocyte chemotactic protein-3, eotaxin, fractalkine, macrophage inflammatory protein-1beta, 6Ckine, IL-8, hemofiltrate CC chemokine-1 and -4, and macrophage-derived chemokine. Chemokine mRNA was generally up-regulated during endometrial receptivity and early pregnancy, particularly of macrophage and natural killer chemoattractants. Chemokine protein was predominantly localized to epithelial glands, whereas differentiated stromal cells were a major source of chemokines after decidualization. This is the first study to use an unbiased approach to screen for endometrial chemokines, and we report the selective regulation of chemokines, corresponding to the recruitment of distinct leukocyte subpopulations required for pregnancy and menstruation.     

Clinical and Immunological Outcome in Cutaneous Leishmaniasis Patients Treated with Pentoxifylline

Pentoxifylline is a tumor necrosis factor-α (TNF-α) inhibitor that also attenuates the immune response and decreases tissue inflammation. The association of pentoxifylline with antimony improves the cure rate of mucosal and cutaneous leishmaniasis. In this randomized and double blind pilot trial, cure rate was higher, although not significant, in patients who received antimony plus pentoxifylline than in those patients receiving antimony plus placebo. A significant decrease in TNF-α and interferon-γ (IFN-γ) levels during therapy was more pronounced in the antimony plus pentoxifylline group, whereas CCL-3 (Chemokine [C-C motif] ligand 3) decreased similarly in both groups. The increased levels of CXCL-9 (Chemokine [C-X-C motif] ligand 9) during therapy were lower in the antimony plus pentoxifylline group. Therapy with pentoxifylline modifies cytokines and chemokines production, which may be associated with therapeutic outcome.     

Production of chemokines in the lungs of infants with severe respiratory syncytial virus bronchiolitis

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in infants is characterized by a massive neutrophilic infiltrate into the airways. Chemokines direct migration of leukocytes and contribute to the pathogenesis of RSV disease. However, little is known about pulmonary chemokine responses to RSV in humans. Our aim was to characterize the production of chemokines in the lungs of infants with RSV bronchiolitis and how this production changes over time. METHODS: Chemokine mRNA and the concentration of chemokines were measured in nonbronchoscopic bronchoalveolar lavage (BAL) samples from infants with RSV bronchiolitis and from control infants. In infants with RSV bronchiolitis, changes in the concentrations of chemokines during the 7 days after intubation and between the days of intubation and extubation were examined. RESULTS: The production of chemokines within the lower respiratory tract was shown in all patients with RSV bronchiolitis. CXC chemokines (particularly CXCL10/interferon-inducible protein 10 and CXCL8/interleukin-8) were found to be the most abundant, but CC chemokines (CCL2/monocyte chemotactic protein 1 and CCL3/macrophage inflammatory protein-1 alpha) were also present. Concentrations of some of these chemokines remained elevated over the course of the illness, whereas others decreased steadily. No differences in the concentrations were found between the days of intubation and extubation. CONCLUSIONS: CXC chemokines predominate within the RSV-infected lung. Much of this response comes from inflammatory cells within the lower respiratory tract. Chemokine response patterns vary over time, possibly indicating different cellular sources for individual chemokines in the RSV-infected lung.     

Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis

BACKGROUND: Chemokine receptors and chemokines have a crucial role in leucocyte recruitment into inflamed tissue. OBJECTIVE: To examine the expression of an extensive number of chemokines and receptors in a unique bank of paired samples of synovial tissue (ST) and peripheral blood (PB) from patients with different forms of arthritis to assist in identifying suitable targets for therapeutic intervention. METHODS: Synovial biopsy specimens were obtained from 23 patients with rheumatoid arthritis (RA), 16 with osteoarthritis, and 8 with reactive arthritis. ST chemokine (CCL2/MCP-1, CCL5/RANTES, CCL7/MCP-3, CCL8/MCP-2, CCL14/HCC-1, CCL15/HCC-2, CCL16/HCC-4), chemokine receptor (CCR1, CCR2b, CCR5, CXCR4), and CD13 expression was analysed by immunohistochemistry and two colour immunofluorescence. Chemokine receptor expression (CCR1, CCR3, CCR5, CCR6, CCR7) on PB cells was studied by flow cytometry. Non-parametric tests were used for statistical analysis. RESULTS: Abundant expression of CCR1, CXCR4, and CCR5 was found in all forms of arthritis, with a specific increase of CCL5 and CCL15 in RA. CCL7, CCL8, CCL14, CCL15, and CCL16 were detected for the first time in ST. The results for PB analysis were comparable among different arthritides. Interestingly, compared with healthy controls, significantly lower expression of CCR1 (p<0.005) and CCR5 (p<0.05) by PB monocytes in the patient groups was seen. DISCUSSION: A variety of chemokines and receptors might have an important role in several inflammatory joint disorders. Although other receptors are involved as well, migration of CCR1(+) and CCR5(+) cells towards the synovial compartment may play a part in the effector phase of various forms of arthritis.     

Regulation of atherosclerotic plaque inflammation

The immune reactions that regulate atherosclerotic plaque inflammation involve chemokines, lipid mediators and costimulatory molecules. Chemokines are a family of chemotactic cytokines that mediate immune cell recruitment and control cell homeostasis and activation of different immune cell types and subsets. Chemokine production and activation of chemokine receptors form a positive feedback mechanism to recruit monocytes, neutrophils and lymphocytes into the atherosclerotic plaque. In addition, chemokine signalling affects immune cell mobilization from the bone marrow. Targeting several of the chemokines and/or chemokine receptors reduces experimental atherosclerosis, whereas specific chemokine pathways appear to be involved in plaque regression. Leukotrienes are lipid mediators that are formed locally in atherosclerotic lesions from arachidonic acid. Leukotrienes mediate immune cell recruitment and activation within the plaque as well as smooth muscle cell proliferation and endothelial dysfunction. Antileukotrienes decrease experimental atherosclerosis, and recent observational data suggest beneficial clinical effects of leukotriene receptor antagonism in cardiovascular disease prevention. By contrast, other lipid mediators, such as lipoxins and metabolites of omega‐3 fatty acids, have been associated with the resolution of inflammation. Costimulatory molecules play a central role in fine‐tuning immunological reactions and mediate crosstalk between innate and adaptive immunity in atherosclerosis. Targeting these interactions is a promising approach for the treatment of atherosclerosis, but immunological side effects are still a concern. In summary, targeting chemokines, leukotriene receptors and costimulatory molecules could represent potential therapeutic strategies to control atherosclerotic plaque inflammation.     

Chemokine receptors and their role in inflammation and infectious diseases

Chemokines are small peptides that are potent activators and chemoattractants for leukocyte subpopulations and some nonhemopoietic cells. Their actions are mediated by a family of 7-transmembrane G-protein-coupled receptors, the size of which has grown considerably in recent years and now includes 18 members. Chemokine receptor expression on different cell types and their binding and response to specific chemokines are highly variable. Significant advances have been made in understanding the regulation of chemokine receptor expression and the intracellular signaling mechanisms used in bringing about cell activation. Chemokine receptors have also recently been implicated in several disease states including allergy, psoriasis, atherosclerosis, and malaria. However, most fascinating has been the observation that some of these receptors are used by human immunodeficiency virus type 1 in gaining entry into permissive cells. This review will discuss structural and functional aspects of chemokine receptor biology and will consider the roles these receptors play in inflammation and in infectious diseases.     

调节性T细胞—动脉粥样硬化治疗的新靶点

动脉粥样硬化(atherosclerosis,AS)是血管壁的一种慢性炎症疾病,免疫系统在其发生发展中起着重要的作用。有研究表明,调节性T(regulatory T,Treg)细胞参与了AS的炎症反应,通过下调其反应可延缓疾病的进程。本文综述了近年有关Treg细胞与AS关系的文献,探讨了Treg细胞在AS发生发展中的重要作用,说明了CD3对Treg细胞增殖的影响及与AS的关系,提出了AS治疗的免疫学新靶点。     

Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis

OBJECTIVE: Zygapophyseal joints of the spine are often affected in ankylosing spondylitis (AS). In this study, we undertook a systematic immunohistologic evaluation of the immunopathology of the zygapophyseal joints in patients with advanced AS. METHODS: We obtained zygapophyseal joints from 16 AS patients undergoing polysegmental correction of kyphosis and from 10 non-AS controls (at autopsy). Immunohistologic analysis of the bone marrow was performed by analyzing the number of infiltrating T cells (CD3, CD4, CD8), B cells (CD20), osteoclasts (CD68), bone marrow macrophages (CD68), and microvessel density (CD34) per high-power field. RESULTS: Zygapophyseal joints from 6 of 16 AS patients, but from none of the controls, exhibited 2 or more CD3+ T cell aggregates, signifying persistent inflammation. Interstitial CD4+ and CD8+ T cells were significantly more frequent in AS patients compared with non-AS controls (P = 0.002 and P = 0.049, respectively). While there was no clear difference between the number of CD20+ B cells in AS patients overall compared with controls, there was a significant difference when persistently inflamed joints from patients with AS were compared with joints without active inflammation from patients with AS or joints from controls (both P = 0.03). Microvessel density in bone marrow from AS patients with active inflammation was significantly higher than that in bone marrow from controls. CONCLUSION: This immunohistologic study of bone marrow from zygapophyseal joints demonstrates persistent inflammation in the spine of patients with AS, including those with longstanding disease. The findings of increased numbers of T cells and B cells and neoangiogenesis suggest that these features play a role in the pathogenesis of AS.