趋化因子FKN与慢性阻塞性肺疾病

慢性阻塞性肺疾病(COPD)的发病机制复杂,炎症起中心环节的作用.趋化因子是一类炎症细胞因子,因其具有趋化和激活白细胞的作用,在机体的炎症反应中起着重要的作用.其中趋化因子FKN属于CX3C亚族,有膜结合形式和可溶性游离形式,参与细胞生长调节、血细胞生成、血管生成、细胞间的黏附、免疫炎症等多种生物学功能.现就趋化因子FKN与慢性阻塞性肺病的关系作一简要概述.     

神经营养素在慢性阻塞性肺疾病中的作用

气道结构细胞、炎性细胞通过自分泌或旁分泌神经营养素(NTs)参与气道高反应、气道炎症、气道重塑,在肺过敏性疾病及炎性疾病中发挥重要作用.目前,NTs及受体在慢性阻塞性肺疾病研究较少,但依然可以证实NTs及受体介导了气道炎症、气道神经源性炎症、气道重塑,从而参与慢性阻塞性肺疾病的发病机制.     

COPD患者血清炎症介质水平在病情评估中的应用价值

正多种炎症介质及炎症细胞参与慢性阻塞性肺疾病(COPD)的发生发展,在白细胞向炎症组织募集过程中,趋化因子作为一种细胞因子发挥着极为重要的作用。相关医学学者研究表明~[1],炎症组织在趋化因子受体3高表达的情况下会有定向迁移及募集发生。本研究探讨了COPD患者血清白细胞介素-6(IL-6)、干扰素-γ(INF-γ)、C反应蛋白(CRP)水平变化在病情评估中的应用价值。     

趋化因子与慢性阻塞性肺疾病

慢性阻塞性肺疾病(COPD)是以慢性气流受限为特征的缓慢进展、渐进加重的肺部疾病。气道慢性炎症,特别是中小气道炎症是其主要病变特征。COPD气道慢性炎症是由复杂的炎性细胞及其分泌的细胞因子相互诱导、相互调节而发生发展的,最终导致气道结构的重构和气流阻塞的形成,在COPD发病中起着十分重要的作用。而炎性细胞趋肺的过程又有赖于多种趋化因子的参与方可完成。很多学者认为趋化因子在COPD患者气道炎症中起了关键性的作用。近年来,随着对COPD气道炎症特点研究的逐渐深入,趋化因子日益成为COPD研究的热点之一。本文就趋化因子在C…     

趋化因子受体 3 在老年 COPD 中的作用简

目的 探讨老年慢性阻塞性肺疾病（COPD）发病机制中趋化因子受体3 （CXCR3）的作用.方法 选择COPD急性加重期、稳定期患者和对照组各30例,分别作为A、B、C组,用流式细胞术进行检测.结果 CD＋4CXCR3＋T细胞占总CD＋4T细胞的百分比及CD＋8CXCR3＋T细胞占总CD＋8T细胞的百分比的比较中,A组治疗前均明显低于B、C组（P均〈0.05）治疗后CD＋4CXCR3＋T细胞占总CD＋4T细胞的百分比、CD＋8CXCR3＋T细胞占总CD＋8T细胞的百分比、CD＋4CXCR3＋T与CD＋8CXCR3＋T细胞MFI相比治疗前均显著下降（P〈0.05）.结论 COPD稳定期T细胞上CXCR3＋表达明显增多,在COPD慢性炎症反应中可能发挥着重要作用.     

趋化因子与慢性阻塞性肺疾病

慢性阻塞性肺疾病（COPD）是以慢性气流受限为特征的缓慢进展、渐进加重的肺部疾病。气道慢性炎症，特别是中小气道炎症是其主要病变特征。COPD气道慢性炎症是由复杂的炎性细胞及其分泌的细胞因子相互诱导、相互调节而发生发展的，最终导致气道结构的重构和气流阻塞的形成，在COPD发病中起着十分重要的作用。而炎性细胞趋肺的过程又有赖于多种趋化因子的参与方可完成。很多学者认为趋化因子在COPD患者气道炎症中起了关键性的作用。近年来，随着对COPD气道炎症特点研究的逐渐深入，趋化因子日益成为COPD研究的热点之一。本文就趋化因子在COPD发病中的作用机制及其临床应用价值作简要综述。     

可溶性髓样细胞触发受体-1在慢性阻塞性肺疾病中作用的研究进展

可溶性髓样细胞触发受体-1(soluble triggering receptor expressed on myeloid cells-1,s TREM-1)是主要表达在中性粒细胞和单核细胞巨噬细胞的膜受体,属于免疫蛋白超家族中的一员,与未知配体结合有放大炎症的作用。慢性阻塞性肺疾病是一种气道的慢性炎症,近年来研究发现s TREM-1在慢性阻塞性肺疾病炎症反复加重、病情迁延中有一定的作用,该文就s TREM-1的结构、信号通路、慢性阻塞性肺疾病的发病机制及s TREM-1在慢性阻塞性肺疾病中的表达进行综述。     

白介素10与慢性阻塞性肺疾病

白介素10(interleukin-10,IL-10)是一个有力的抗炎和免疫调节因子,在体内炎症反应过程中发挥着重要的作用.它通过抑制炎症因子和细胞趋化因子的合成、抑制细胞介导的免疫反应,从而起到抗炎和免疫调节作用.本文就IL-1O的分子生物学特点、细胞分布及IL-1O与慢性阻塞性肺疾病的关系作一综述.     

趋化因子受体CCR7与类风湿关节炎

根据基因及蛋白质结构，趋化因子分为4型(CXC，CC．CX3C及C型),趋化因子受体也分为4型，它们表达于不同的细胞，在炎症的发生、发展过程中起着重要作用。类风湿关节炎(rheumatoid arthritis，RA)是一种慢性自身免疫性炎症，炎症关节局部有大量淋巴细胞和树突状细胞(DC)浸润。研究表明多种趋化因子及其受体参与此过程。CCR7是一种表达于天然和活化T细胞上的G蛋白耦联受体．     

T细胞及其细胞因子与慢性阻塞性疾病

慢性阻塞性肺疾病（COPD）是引起人类发病和死亡的主要原因之一。大量的研究表明,在COPD患者的气道、肺实质和肺血管中均存在着慢性炎症、T细胞、中性粒细胞和嗜酸粒细胞参与炎症过程,但这些细胞在COPD发病中的确切作用仍不十分清楚。本文就T细胞及其细胞因子在COPD中的变化作用以及吸烟对T细胞及其细胞因子的影响做一综述。     

Pathophysiology of exacerbations of chronic obstructive pulmonary disease

Smokers with stable chronic obstructive pulmonary disease have a chronic inflammation of the entire tracheobronchial tree characterized by an increased number of macrophages and CD8 T lymphocytes in the airway wall and of neutrophils in the airway lumen. Exacerbations of chronic obstructive pulmonary disease are considered to reflect worsening of the underlying chronic inflammation of the airways, caused mainly by viral and bacterial infections and air pollution. During exacerbations, the inflammatory cellular pattern changes, with a further increase of eosinophils and/or neutrophils and various inflammatory mediators--for example, cytokines (tumor necrosis factor-alpha, RANTES [regulated upon activation normal T cell-expressed and secreted], and eotaxin-1), chemokines (CXCL5 [ENA-78], CXCL8), chemokine receptors (CCR3, CXCR1, and CXCR2), adhesion molecules (E-selectin and ICAM-1), and markers of oxidative stress (H(2)O(2) and 8-isoprostane, glutathione depletion). Worsening of inflammation is considered responsible for the deterioration of lung function and clinical status during exacerbations.     

Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease

CXCR3 is a chemokine receptor preferentially expressed on lymphocytes, particularly on type-1 T-lymphocytes. Smokers who develop chronic obstructive pulmonary disease (COPD) have a chronic bronchopulmonary inflammation that is characterized by an increased infiltration of T-lymphocytes, particularly CD8(+), in the airways and lung parenchyma. To investigate the expression of CXCR3 and its ligand interferon-induced protein 10/CXCL10 in COPD, we counted the number of CXCR3(+) cells and analyzed the expression of CXCL10 in the peripheral airways of 19 patients undergoing lung resection for localized pulmonary lesions. We examined lung specimens from seven smokers with fixed airflow limitation (COPD), five smokers with normal lung function, and seven nonsmoking subjects with normal lung function. The number of CXCR3(+) cells was immunohistochemically quantified in the epithelium, in the submucosa, and in the adventitia of peripheral airways. The number of CXCR3(+) cells in the epithelium and submucosa was increased in smokers with COPD as compared with nonsmoking subjects, but not as compared with smokers with normal lung function. Immunoreactivity for the CXCR3-ligand CXCL10 was present in the bronchiolar epithelium of smokers with COPD but not in the bronchiolar epithelium of smoking and nonsmoking control subjects. Most CXCR3(+) cells coexpressed CD8 and produced interferon gamma. These findings suggest that the CXCR3/CXCL10 axis may be involved in the T cell recruitment that occurs in peripheral airways of smokers with COPD and that these T cells may have a type-1 profile.     

老年慢性阻塞性肺疾病患者外周血T细胞表达趋化因子受体3的研究

目的 探讨趋化因子受体3(CXCR3)在老年慢性阻塞性肺疾病(COPD)发病中的作用.方法 研究对象均为65岁以上的老年人,分为COPD急性加重期组(20例)、COPD稳定期组(17例)及对照组(14例),分离外周血单个核细胞,流式细胞仪检测CD4+和CD8+T细胞分别占总T细胞的百分比,CD4+CXCR3+T细胞占总CD4+T细胞的百分比,CD8+CXCR3+T细胞占总CD8+T细胞的百分比,以及CD4+CXCR3+和CD8+CXCR3+T细胞上CXCR3的平均荧光强度(MFI).结果 ①三组间及COPD急性加重期组治疗前后CD4+、CD8+T细胞分别占总T细胞的百分比,差异无统计学意义.②CD8+CXCR3+T细胞占总CD8+T细胞的百分比及CD4+CXCR3+T细胞占总CD4+T细胞百分比:COPD急性加重期组较COPD稳定组及对照组明显降低,COPD稳定组较对照组明显升高,差异有统计学意义,P＜0.05.CD4+CXCR3+和CD8+CXCR3+T细胞上CXCR3的MFI三组间差异无统计学意义.③COPD急性加重期组经治疗后CD8+CXCR3+T细胞占总CD8+T细胞的百分比及CD4+CXCR3+T细胞占总CD4+T细胞百分比,CD4+CXCR3+和CD8+CXCR3+T细胞上CXCR3的MFI,均明显降低,差异有统计学意义,P＜0.05.结论 COPD稳定期T细胞上CXCR3的过度表达在COPD慢性炎症过程中起作用.     

Differential effect of methotrexate on the increased CCR2 density on circulating CD4 T lymphocytes and monocytes in active chronic rheumatoid arthritis, with a down regulation only on monocytes in responders

OBJECTIVES: To evaluate the effect of orally administered methotrexate (MTX) on the density of CC chemokine receptor 2 (CCR2) and CXC chemokine receptor 3 (CXCR3) on circulating monocytes, and the coexpression of CXCR3 and CCR2 on CD4 T lymphocytes in patients with active chronic rheumatoid arthritis. METHODS: All 34 patients with rheumatoid arthritis fulfilled the 1987 American Rheumatism Association criteria and were followed for 16 weeks after starting MTX. Peripheral blood mononuclear cells were analysed for CCR2 and CXCR3 density by three-colour flow cytometry before initiation of MTX and at week 12. RESULTS: 22 (65%) patients were non-responders, 12 (35%) patients responded to MTX by American College of Rheumatology (ACR)20% criteria, and 8 (24%) of these patients responded by ACR50%. In patients with active rheumatoid arthritis before starting MTX, CCR2 density on circulating monocytes, CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was increased compared with controls. During 12 weeks of MTX treatment, the CCR2 density on monocytes decreased significantly in the ACR50% group but not in the ACR20% and non-responder groups. The increased CCR2 density on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was unaffected by the reduction in disease activity measured in relation to MTX treatment. The percentage of both monocytes and CD4(+) CXCR3(+) and CD4+ CXCR3(-) T lymphocytes among the peripheral circulating mononuclear cells did not change during MTX treatment. CONCLUSIONS: Active chronic rheumatoid arthritis is characterised by enhanced CCR2 density on circulating monocytes and CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes. During MTX treatment, a decrease in CCR2 density on monocytes in the ACR50% responder group was associated with decreased disease activity. The increased CCR2 density on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was uninfluenced by MTX and disease activity.     

Modification of surface antigens in blood CD8+ T-lymphocytes in COPD: effects of smoking.

In contrast to the effects of cigarette smoke on T-lymphocyte subsets in the airways, it has not yet been determined whether smoking has immunomodulatory effects on surface antigens of peripheral blood T-lymphocytes and, if that is the case, whether these effects differ in smokers with and without chronic obstructive pulmonary disease (COPD). The present authors have, therefore, examined the expression of the surface activation marker CD28, the levels of cytotoxic effector lymphocytes (CD27-/CD45RA+) and the expression of the lung type (Tc)1-specific chemokine receptor CXCR(3)+ on peripheral blood CD8+ T-lymphocytes. The present authors have also studied the chemotactic activity of CD8+ T-lymphocytes on monocyte chemotactic protein (MCP)-1 and compared 13 nonsmoking controls, 12 smokers with COPD and 14 smokers without airflow limitation. There was a decrease in the total count of CD8+ T-cells and an increase in the CD4+/CD8+ ratio in smokers with COPD compared with smokers without COPD and controls. Expression of the Tc1-specific chemokine receptor CXCR(3)+ by CD8+ T-cells was increased in smokers with COPD compared with smokers without COPD and controls. The expression of activated and of cytotoxic effector CD8+ T-cells in smokers with and without COPD showed an increase compared with controls. CD8+ T-cells from smokers with and without COPD showed a decrease in chemotactic activity to MCP-1 compared with controls. In conclusion, chronic obstructive pulmonary disease may be a systemic immunomodulatory disease associated with the modification of surface antigens in blood CD8+ T-lymphocytes.     

COPD相关T淋巴细胞亚群的新功能

肺部慢性非特异性炎症被认为是COPD发生发展的病理基础,淋巴细胞在调节 COPD气道炎症中发挥重要的作用.研究发现,效应T细胞、抑制性 T细胞与耗竭 T细胞三者在 COPD的炎症调节中发挥着不同的正负调节效应,它们分化上互相关联,功能上互相拮抗,一旦发生免疫失衡,可加重气道结构的破坏、加速COPD的进展和恶化.     

Pathogenesis of chronic obstructive pulmonary disease

The current paradigm for the pathogenesis of chronic obstructive pulmonary disease is that chronic airflow limitation results from an abnormal inflammatory response to inhaled particles and gases in the lung. Airspace inflammation appears to be different in susceptible smokers and involves a predominance of CD8+ T lymphocytes, neutrophils, and macrophages. Studies have characterized inflammation in the peripheral airspaces in different stages of disease severity. Two other processes have received considerable research attention. The first is a protease-antiprotease imbalance, which has been linked to the pathogenesis of emphysema. However, the hypothesis of an increased protease burden associated with functional inhibition of antiproteases has been difficult to prove and is now considered an oversimplification. The second process, oxidative stress, has a role in many of the pathogenic processes of chronic obstructive pulmonary disease and may be one mechanism that enhances the inflammatory response. In addition, it has been proposed that the development of emphysema may involve alveolar cell loss through apoptosis. This mechanism may involve the vascular endothelial growth factor pathway and oxidative stress.     

Expression and regulation of the chemokine receptor CXCR3 on lymphocytes from normal and inflammatory bowel disease mucosa

Chemokine receptors play an important role in the recruitment of activated T cells to inflammatory sites. The aim of this study was to analyze the expression of the chemokine receptor CXCR3 on T lymphocytes in intestinal lymphoid tissues and to document the altered disposition of these cells in patients with inflammatory bowel disease (IBD). The expression and regulation of CXCR3 on mucosal lymphoid tissue and peripheral blood lymphocytes (PBLs) were analyzed by flow cytometry and Northern blotting. The migration of lamina propria lymphocytes (LPLs) and PBLs to interferon (IFN)-gamma-inducible protein (IP)-10 (or CXCL10) was evaluated by chemotaxis assays. IFN-gamma and interleukin-4-producing T lymphocytes were quantitated by intracellular staining, and IFN-gamma was measured in culture supernatants by enzyme-linked immunosorbent assay. CXCR3 is expressed on the majority of CD4 lamina propria (LP) T cells and correlates with a T-helper (Th) type 1/Th-0 cytokine phenotype on LP and mesenteric lymph node (MLN) CD4 T lymphocytes. IP-10/CXCL10 is more chemotactic in vitro for both CD4 and CD8 T cells that have been isolated from the LP compared with peripheral blood. CXCR3 protein, but not messenger RNA, expression was lower in inflamed LPLs compared with uninvolved LPLs in patients with ulcerative colitis but not in those with Crohn's disease. However, CXCR3 was expressed on a higher percentage of MLN CD4 T cells isolated from inflamed intestinal tissue, and CXCR3 expression could be induced in vitro with T-cell activation in MLN CD4 T cells. In summary, most CXCR3 T lymphocytes in normal intestinal tissues are Th-1/Th-0 effector/memory cells. Activation-dependent receptor regulation and alteration in receptor-bearing cells, primarily in MLN draining inflamed intestinal tissue, suggest an important role for this T-cell subset in the pathogenesis of human IBD.     

Smoking: relationship to chronic bronchitis, chronic obstructive pulmonary disease and mortality

PURPOSE OF REVIEW: To describe the recent findings concerning the relationship between smoking, chronic bronchitis, chronic obstructive pulmonary disease and mortality. RECENT FINDINGS: During their lifetime, over 40% of smokers develop chronic bronchitis. Chronic bronchitis is associated with an accelerated decline in lung function - a risk of developing chronic obstructive pulmonary disease and mortality. Approximately one-quarter of smokers can be affected by clinically significant chronic obstructive pulmonary disease. The incidence of chronic obstructive pulmonary disease is also substantial in young adults. Smokers may reduce their risk of developing chronic obstructive pulmonary disease by physical activity and increase their survival by smoking reduction. In adults and the elderly population, severe chronic obstructive pulmonary disease is associated with the most rapid decline in lung function, which is, in turn, associated with chronic obstructive pulmonary disease-related hospitalization and mortality. Using a fixed forced expiratory volume in 1 s/force vital capacity ratio (0.7) to define obstruction in chronic obstructive pulmonary disease at old age is acceptable. In chronic obstructive pulmonary disease patients, the disease is still underreported on death certificates. Chronic mucus production and being a female are associated with chronic obstructive pulmonary disease mentioned on death certificates. SUMMARY: Chronic bronchitis is a marker identifying high-risk individuals. With respect to chronic obstructive pulmonary disease and mortality, interventions to promote smoking cessation are important to reduce these risks.     

The expression of chemokine receptor CXCR3: relevance to disease activity of rheumatoid arthritis

 CXC chemokine receptor 3 (CXCR3) is selectively expressed on T helper 1 (Th1) type T cells and has been shown to be responsible for Th1-dominant immune responses. In this study, we analyzed the expression of CXCR3 on peripheral blood T lymphocytes of patients with rheumatoid arthritis (RA) by FACS analysis using antihuman CXCR3 monoclonal antibody and determined the clinical relevance in this disease. Significantly higher expression of CXCR3 was found on peripheral blood CD4+ T lymphocytes of RA patients than healthy controls. The CXCR3 expression in RA patients with a high erythrocyte sedimentation rate was significantly higher than in those with a low erythrocyte sedimentation rate. Moreover, we found that the CXCR3 expression in RA patients with long-term disease duration was significantly higher than in those with short-term disease. On the other hand, CC chemokine receptor 4 (CCR4), which was shown to be selectively expressed on Th2-type T cells, was expressed at low levels in RA patients as well as in healthy controls. The serum level of interleukin (IL)-18 in RA patients was higher than that in healthy controls, although there was no statistically significant difference. This study suggests that the Th1 immune response is predominant in RA and that CXCR3 may have relevance in regard to the disease course in RA patients. Received: January 28, 2002 / Accepted: August 14, 2002