Chemokines: therapeutic targets for autoimmune and inflammatory renal disease
Chemokines: therapeutic targets for autoimmune and inflammatory renal disease
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DOI：
10.1007/s00281-003-0124-4
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发表时间：
2003-05-01
期刊：
影响因子：
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通讯作者：
Rovin, BH
中科院分区：
文献类型：
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作者：
Kelley, VR;Rovin, BH
趋化因子是小分子(8-12 kDa)的趋化细胞因子。在炎症过程中，趋化因子在协调白细胞迁移方面起着至关重要的作用。丰富的趋化因子及其受体几乎渗透到免疫学的各个方面，已发展到包括大约50个配体和20个G蛋白偶联受体[14，25，57]。最初，趋化因子被发现是因为它们出现在炎症过程中。最近，趋化因子的作用范围扩大了，因为趋化因子的结构性表达已被证明可以调节体内平衡功能。根据N末端附近半胱氨酸残基的构型对趋化因子进行分类，简化了令人望而生畏的趋化因子清单。有四个趋化因子家族：CC、CXC、C和CX3C。因此，在CXC趋化因子中，初级氨基酸序列中的前两个半胱氨酸残基被一个氨基酸分开，而在CC趋化因子中，这些半胱氨酸残基是相邻的。CXC和CC趋化因子是迄今为止最大的亚家族。趋化因子调节白细胞在经历病变的组织部位的部署。白细胞遵循趋化因子的梯度。趋化因子是在病理性挑战过程中在细胞中诱导的。白细胞渗入组织是一个多步骤的过程，涉及到选择素、整合素和趋化因子。白细胞通过与选择素结合而松散地附着在血管壁上，选择素是在绝对压力下专门用于黏附的分子。趋化因子激活整合素，这是第二组黏附分子。被激活的整合素经历了结构/构象的变化，这些变化增加了它们的亲和力，导致白细胞牢固地锚定在血管壁上，并使白细胞跨内皮细胞迁移。由于白细胞负责组织损伤，而趋化因子的释放是白细胞从血液进入组织所必需的，因此阻断趋化因子应该可以预防炎症和自身免疫性疾病。
Chemokines are small (8–12 kDa) chemoattractant cytokines. During inflammation chemokines are crucial in orchestrating leukocyte migration. The rich repertoire of chemokines, and their receptors, permeates nearly every aspect of immunology and has grown to comprise approximately 50 ligands, and 20 G protein-coupled receptors [14, 25, 57]. Initially, chemokines were discovered because they appeared during inflammation. More recently the scope of the role of chemokines has expanded as constitutive expression of chemokines has been shown to regulate homeostatic functions. The daunting list of chemokines is simplified by categorizing them according to the configuration of cysteine residues near the N terminus. There are four chemokine families: CC, CXC, C and CX3C. Thus, in CXC chemokines the first two cysteine residues in the primary amino acid sequence are separated by a single amino acid, whereas in the CC chemokines these cysteine residues are adjacent. The CXC and CC chemokines are by far the largest subfamilies. Chemokines regulate the deployment of leukocytes to tissue sites undergoing pathological change. Leukocytes follow a chemokine gradient. Chemokines are induced in cells during pathological challenge. Extravasation of leukocytes into tissues is a multi-step process involving selectins, integrins and chemokines. Leukocytes loosely adhere to vascular walls by binding to selectins, molecules specialized for adhesion during sheer stress. Chemokines activate integrins, a second group of adhesion molecules. The activated integrins undergo structural/conformational changes that increase their affinity, resulting in firm anchoring of leukocytes to the vessel wall and transmigration of leukocytes across the endothelium. Because leukocytes are responsible for tissue injury, and chemokine release is required for the movement of leukocytes from the blood into tissues, blocking chemokines should prevent inflammation and autoimmune diseases.