Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. Both CD4+ and CD8+ T-lymphocytes play a key role in COPD pathogenesis, but cytokine profiles in circulating T-lymphocytes have not been well characterised. Here we report the analysis of peripheral blood T-cells from 30 stable COPD patients and 10 healthy never-smokers for interferon (IFN)-γ, interleukin (IL)-4, tumour necrosis factor (TNF)-α and the T-helper 17 cytokines IL-17A, IL-17F and IL-22 by intracellular flow cytometry. We found significantly increased proportions of IFN-γ+ and TNF-α+ CD8+ T-cells in COPD patients, when compared with healthy controls. This was most evident in patients with less severe disease. In contrast, expression profiles in circulating CD4+ T-cells were similar in COPD patients and healthy controls for all cytokines tested, except for IL-17F. COPD patients with more severely reduced diffusing capacity had lower proportions of IL-17A+ CD4+ T-cells. Proportions of IL-22+ cells in the CD4+ memory T-cell population were significantly increased in active smokers, when compared with past smokers. Collectively, this comprehensive cytokine analysis of circulating T-cells in COPD patients revealed a correlation for CD8+ T-cells between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and IFN-γ or TNF-α expression, but not for CD4+ T-cells.     

炎性因子在慢性阻塞性肺疾病气道炎症中的作用

COPD是一种以气道慢性炎症为特征之一的慢性呼吸系统疾病,气道炎性反应在COPD占有重要作用。炎性细胞因子是机体内最重要的一类细胞因子,多种炎性细胞因子参与气道炎症的病理生理机制,对肺组织和支气管产生损害,并发肺外效应。在COPD的自然病程中存在炎性细胞因子网络系统,调控COPD的气道炎症的发生发展。     

间充质干细胞移植治疗慢性阻塞性肺疾病的相关研究进展

慢性阻塞性肺疾病(COPD)是一种重要的慢性呼吸系统疾病,主要包括慢性支气管炎和肺气肿,患病人数多,病死率高,由于其缓慢进行性发展,COPD是以上调炎症过程导致诸如上皮细胞凋亡、终末肺泡间隔及肺泡外基质蛋白水解事件发生为特征,严重影响患者的劳动能力和生活质量.近来一些研究揭示,间充质干细胞对肺组织的修复和再生有重要作用...     

炎性细胞因子在慢性阻塞性肺疾病发病机制中的作用

COPD是威胁人类健康的重要疾病,其分子生物学机制一直以来都是研究的重点,慢性炎症反应是其重要的病因病机,炎症因子在慢性炎症反应其中起到重要作用,主要有白介素家族、肿瘤坏死因子、生长因子、黏附因子、血清脂连素、C反应蛋白等。近年来许多学者对此方面进行了研究,本文就这些因子在COPD炎症反应中的作用进行总结。     

IL-21与COPD发病机制的研究进展

IL-21是近年来发现的一种细胞因子,主要由活化的 CD4+T 细胞产生,在 Th17细胞中大量分泌,IL-21与其受体结合后,参与免疫应答与炎症反应.COPD是一种由吸烟所诱发的 T 细胞介导的炎症及自身免疫性的疾病.COPD的发病机制复杂,其中免疫失衡在 COPD发生发展中起着重要作用,多种细胞因子的变化与 COPD有关,IL-21就是其中的一种.本文就 IL-21与 COPD 的气道炎症、肺气肿、肺动脉高压的发病机制的研究作一综述.     

Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by an excessive inflammatory response to inhaled particles, mostly tobacco smoking. Although inflammation is present in all smokers, only a percentage of them develop COPD. T-lymphocytes are important effector and regulatory cells that participate actively in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes. The latter represent a small percentage of the total T-cell population, but play a key role in tissue repair and mucosal homeostasis. To investigate TCR-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes in COPD, the present authors determined, by flow cytometry, the distribution of both subpopulations in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from patients with COPD, smokers with normal lung function and never-smokers. The present study found that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was similar in all three groups; 2) compared with nonsmokers, gamma delta T-lymphocytes were significantly increased in smokers with preserved lung function; and 3) this response was blunted in patients with COPD. These results highlight a novel, potentially relevant, pathogenic mechanism in chronic obstructive pulmonary disease.     

Pulmonary epithelium, cigarette smoke, and chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease involving a wide variety of cells and inflammatory mediators. The most important etiological factor in the development of this disease is cigarette smoking. Much of the research into the mechanisms of COPD has been concerned with the induction of inflammation and the role of neutrophils and macrophages in the pathophysiology of the disease. The possible contribution of the epithelium to the development of COPD has only recently become apparent and remains unclear. In this article we review research into the effect of cigarette smoke on the pulmonary epithelium with particular emphasis on oxidative stress, proteolytic load, pro-inflammatory cytokine and chemokine profile and epithelial secretions. In addition, we have also reviewed how cigarette smoke may affect epithelial damage and repair processes.     

脂联素与慢性阻塞性肺疾病相关性研究进展

脂联素是脂肪组织分泌的一种新的细胞因子,临床研究已证实其参与了能量代谢过程,与炎症标志物具有相关性,慢性阻塞性肺疾病为一慢性炎症过程,随着病情的进展,出现营养不良,因此考虑脂联素参与了慢性阻塞性肺疾病的病理生理过程.现将脂联素与慢性阻塞性肺疾病关系的研究进展综述如下.     

中性粒细胞在慢性阻塞性肺疾病中的作用

慢性阻塞性肺疾病(chronic obstructive pneumonia discase,COPD)是以不完全可逆的气流受限为特征的慢性炎症性疾病.中性粒细胞可能在COPD的发展过程中发挥主要作用.活化的中性粒细胞释放蛋白酶、活性氧和细胞因子,引起肺组织损伤,最终导致气道黏液高分泌,气流受限和肺气肿.     

Increased number of B-cells in bronchial biopsies in COPD.

Recently, it has been shown that the accumulated volume of B-cells in small airways is increased in chronic obstructive pulmonary disease (COPD) Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 3 and 4. Little is known about the number of B-cells in central airways in COPD. The present authors hypothesised that the number of B-cells in bronchial biopsies of large airways is higher in patients with COPD than in controls without airflow limitation and higher in more severe COPD. Therefore, bronchial biopsies were collected from 114 COPD patients (postbronchodilator forced expiratory volume in one second (FEV1) 63+/-9 % predicted value, FEV1/inspiratory vital capacity (IVC) 48+/-9%) and 28 controls (postbronchodilator FEV1 108+/-12 % predicted value, FEV1/IVC 78+/-4%). Paraffin sections were stained for B-cells (CD20+) and their number was determined in the subepithelial area (excluding muscle, glands and vessels). B-cell numbers were higher in patients with COPD versus controls (8.5 versus 3.9 cells x mm(-2), respectively) and higher in patients with GOLD severity stage 3 (n = 11) than stage 2 (n = 103; 22.3 versus 7.8 cells x mm(-2)). No relationship was found between the number of B-cells and clinical characteristics within the chronic obstructive pulmonary disease group. The authors suggest that these increased B-cell numbers may have an important contribution to the pathogenesis of chronic obstructive pulmonary disease.     

炎性细胞因子与慢性阻塞性肺疾病关系的研究进展

慢性阻塞性肺疾病(COPD)是呼吸系统常见疾病,但其确切发病机制目前尚不十分清楚,多种炎性细胞及炎性细胞因子参与的慢性炎性反应被认为是其核心病理改变。本文从常见炎性细胞因子的生物学特性、生物学功能及其与COPD的关系等进行综述。     

Does leptin play a cytokine-like role within the airways of COPD patients?

The leptin-leptin receptor system might be up-regulated in the airways of chronic obstructive pulmonary disease (COPD). In bronchial biopsies obtained from normal subjects and smokers, with and without COPD, the present study examined leptin and leptin-receptor expression and their co-localisation in airway and inflammatory cells. Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end-labelling techniques, apoptosis in airway and inflammatory cells and in leptin and leptin-receptor expressing cells was investigated. In the epithelial cells both leptin and leptin-receptor expression was higher in normal subjects than in smokers and COPD subjects. By contrast, in the sub-mucosa, leptin was over-expressed in COPD when compared with normal subjects and smokers. Leptin and its receptor were co-localised, mainly with activated T cells (CD45R0) and CD8+ T lymphocytes. In smokers, apoptosis was found in some inflammatory cells, whereas in COPD inflammatory cells, leptin and leptin-receptor positive cells were not apoptotic. Leptin expression was related to COPD severity and assessed using the Global initiative for Chronic Obstructive Lung Disease classification. In conclusion, the present study shows an increased leptin expression in bronchial mucosa of chronic obstructive pulmonary disease patients, associated with airway inflammation and airflow obstruction.     

血管内皮生长因子与慢性阻塞性肺疾病

慢性阻塞性肺疾病是一个发病率和死亡率都很高的慢性疾病，其发病机制涉及肺内细胞的凋亡，肺实质细胞的减少，炎性细胞的浸润和气道、血管的重构。血管内皮生长因子作为一个可特异作用于内皮细胞，调节血管内皮细胞生长、分化、修复及发挥功能的重要因子，与慢性阻塞性肺疾病的发生有着密切的联系。     

吸烟、肿瘤坏死因子及其受体与慢性阻塞性肺疾病

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)发病率高.发病机制不清.外界环境的刺激导致气道和血管损伤与修复的失平衡可能与COPD的发生相关.其中吸烟致细胞因子、炎症细胞及炎症介质增多,气道和肺实质慢性炎症,导致气道损伤和重构.最终导致气流受限,在肺气肿的形成中起主要作用.肿瘤坏死因子a是重要的炎症因子,通过其主要受体肿瘤坏死因子受体1参与COPD的形成,在COPD的发生、发展中起重要作用.     

特异性和非特异性免疫细胞在COPD发病机制中的作用

COPD是一种暴露于有害气体或颗粒而导致的持续性气流受限,呈进行性发展,不完全可逆的慢性气道及肺部炎症.COPD是许多炎症通路介导的复杂病理过程,是成年人发病及病死的主要原因之一.巨噬细胞、中性粒细胞、树突状细胞、CD8+T和CD4+T细胞亚群是COPD发病过程中的主要炎症细胞,这些炎症细胞与人体疾病研究还不清楚,是如何参与宿主防御,免疫调节和自身免疫作用有待进一步研究.本文旨在对各种炎症细胞及在COPD免疫机制中的作用作一综述.     

New insights into the immunology of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome associated with abnormal inflammatory immune responses of the lung to noxious particles and gases. Cigarette smoke activates innate immune cells such as epithelial cells and macrophages by triggering pattern recognition receptors, either directly or indirectly via the release of damage-associated molecular patterns from stressed or dying cells. Activated dendritic cells induce adaptive immune responses encompassing T helper (Th1 and Th17) CD4+ T cells, CD8+ cytotoxicity, and B-cell responses, which lead to the development of lymphoid follicles on chronic inflammation. Viral and bacterial infections not only cause acute exacerbations of COPD, but also amplify and perpetuate chronic inflammation in stable COPD via pathogen-associated molecular patterns. We discuss the role of autoimmunity (autoantibodies), remodelling, extracellular matrix-derived fragments, impaired innate lung defences, oxidative stress, hypoxia, and dysregulation of microRNAs in the persistence of the pulmonary inflammation despite smoking cessation.     

Aspergillus infection in chronic obstructive pulmonary diseases

Chronic obstructive pulmonary disease (COPD) is a chronic airway non-specific inflammatory disease characterised by airway obstruction and alveolar destruction. In recent years, due to the extensive use of antibiotics, glucocorticoids, immunosuppressants and other drugs, pulmonary fungal infection in patients with AECOPD, especially aspergillus infection, has gradually increased. The forms of aspergillus infection present in COPD patients include sensitisation, chronic pulmonary aspergillosis (CPA) and invasive pulmonary aspergillosis (IPA). This review will summarise diagnostic and treatment of aspergillus in COPD patients.     

Bronchial epithelial cells: The key effector cells in the pathogenesis of chronic obstructive pulmonary disease?

The primary function of the bronchial epithelium is to act as a defensive barrier aiding the maintenance of normal airway function. Bronchial epithelial cells (BEC) form the interface between the external environment and the internal milieu, making it a major target of inhaled insults. However, BEC can also serve as effectors to initiate and orchestrate immune and inflammatory responses by releasing chemokines and cytokines, which recruit and activate inflammatory cells. They also produce excess reactive oxygen species as a result of an oxidant/antioxidant imbalance that contributes to chronic pulmonary inflammation and lung tissue damage. Accumulated mucus from hyperplastic BEC obstructs the lumen of small airways, whereas impaired cell repair, squamous metaplasia and increased extracellular matrix deposition underlying the epithelium is associated with airway remodelling particularly fibrosis and thickening of the airway wall. These alterations in small airway structure lead to airflow limitation, which is critical in the clinical diagnosis of chronic obstructive pulmonary disease (COPD). In this review, we discuss the abnormal function of BEC within a disturbed immune homeostatic environment consisting of ongoing inflammation, oxidative stress and small airway obstruction. We provide an overview of recent insights into the function of the bronchial epithelium in the pathogenesis of COPD and how this may provide novel therapeutic approaches for a number of chronic lung diseases.