Role of the CX3CL1-CX3CR1 axis in chronic inflammatory lung diseases.
Role of the CX3CL1-CX3CR1 axis in chronic inflammatory lung diseases.
复制标题
DOI：
--
复制
发表时间：
2010-08
影响因子：
0.1
通讯作者：
Jianliang Zhang;J. Patel
中科院分区：
文献类型：
--
作者：
Jianliang Zhang;J. Patel
慢性阻塞性肺疾病(COPD)和肺动脉高压等肺部疾病患者常存在持续性炎症。循环中的白细胞通过肺血管内皮细胞的迁移有助于这些慢性肺部疾病的结构破坏和重塑。炎性趋化因子CX3CL1/Fractalkine与炎症性肺部疾病相关。膜锚定的CX3CL1作为一种黏附分子，捕捉表达唯一受体CX3CR1的单核白细胞亚群。CX3CL1的胞外趋化因子结构域可以被刺激暴露细胞中的去整合素和金属蛋白酶结构域(ADAM)切割/脱落。可溶性CX3CL1可趋化和激活CX3CR1+白细胞，如CD8+、CD4+和γδT淋巴细胞、自然杀伤细胞、树突状细胞和单核/巨噬细胞。CX3CR1+白细胞附着于肺血管内皮细胞并通过肺血管内皮细胞迁移，导致单个核细胞在肺血管壁和实质内聚集。渗入的CX3CR1+免疫细胞可释放介质诱导损伤、刺激增殖和/或趋化吸引炎症细胞。这在炎症性肺部疾病的发展中促进了结构的破坏和重塑。在治疗慢性肺部疾病相关的肺功能下降方面取得的有限临床成功表明，了解触发炎症的上游信号的紧迫性和重要性。本文就CX3CL1-CX3CR1轴介导的单核白细胞黏附和迁移在慢性阻塞性肺疾病、肺动脉高压等炎症性肺疾病中的研究进展作一综述。更好地了解循环中的白细胞不断流入肺血管壁和肺实质将有助于为开发新的治疗方法来治疗甚至治愈包括COPD和肺动脉高压在内的慢性肺部疾病奠定基础。
Persistent inflammation is often present in patients with lung diseases such as chronic obstructive pulmonary diseases (COPD) and pulmonary hypertension. Circulatory leukocyte migration through the lung vascular endothelium contributes to the structural destruction and remodeling seen in these chronic lung diseases. An inflammatory chemokine CX3CL1/fractalkine is associated with inflammatory lung diseases. Membrane-anchored CX3CL1 serves as an adhesion molecule to capture subsets of mononuclear leukocytes that express the sole receptor, CX3CR1. The extracellular chemokine domain of CX3CL1 can be cleaved/shed by a disintegrin and metalloproteinase domain (ADAM) from stimulus-exposed cells. Soluble CX3CL1 chemoattracts and activates CX3CR1+ leukocytes such as CD8+, CD4+, and γδ T lymphocytes, natural killer cells, dendritic cells, and monocytes/macrophages. CX3CR1+ leukocyte attachment to and migration through the lung vascular endothelium lead to mononuclear cell accumulation in the lung vessel walls and parenchyma. Infiltrated CX3CR1+ immune cells can release mediators to induce injury, stimulate proliferation, and/or chemoattract inflammatory cells. This contributes to structural destruction and remodeling in the development of inflammatory lung diseases. Limited clinical success in treating chronic pulmonary diseases-associated lung functional decline indicates the urgency and significance of understanding upstream signaling that triggers inflammation. This article reviews the advances in the CX3CL1-CX3CR1 axis-mediated modulation of mononuclear leukocyte adhesion and migration in inflammatory lung diseases such as COPD and pulmonary hypertension. Better understanding of the constant flow of circulating leukocytes into the lung vessel wall and parenchyma will help set a stage for the development of novel therapeutic approaches to treat or even cure chronic lung diseases including COPD and pulmonary hypertension.