Cascieri M A, Springer M S
Department of Immunology and Rheumatology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Curr Opin Chem Biol. 2000 Aug;4(4):420-7. doi: 10.1016/s1367-5931(00)00113-7.
The chemokines are a large superfamily of chemotactic cytokines that are utilized to direct the trafficking and migration of leukocytes within the immune system. The chemokines mediate their activity through a large family of G-protein-coupled receptors, and thus are highly tractable as therapeutic targets. Exciting advances have been made in the field within the past year, not the least of which is the disclosure of potent antagonists of several chemokine receptors. Several CCR5 antagonists have demonstrated potent antiviral activity and may represent novel therapeutic agents for the treatment of AIDS. In addition, new biological insights have been gained from the demonstration that the targeting of cells to inflammatory sites is tissue specific, such that different chemokine/chemokine-receptor pairs are utilized in recruitment of T-lymphocytes to the skin and to the intestine. Also, utilization of neutralizing antibodies to the CXCR3 ligand Mig in murine allograft transplantation models has demonstrated the importance of CXCR3 in orchestrating T-cell-mediated tissue rejection.
趋化因子是趋化性细 胞因子的一个大家族，用于指导白细胞在免疫系统内的运输和迁移。趋化因子通过一大类G蛋白偶联受体介导其活性，因此作为治疗靶点具有高度的可操作性。过去一年该领域取得了令人振奋的进展，其中最重要的是几种趋化因子受体强效拮抗剂的披露。几种CCR5拮抗剂已显示出强效抗病毒活性，可能代表治疗艾滋病的新型治疗药物。此外，通过证明细胞向炎症部位的靶向是组织特异性的，从而获得了新的生物学见解，即在T淋巴细胞募集到皮肤和肠道的过程中使用了不同的趋化因子/趋化因子受体对。此外，在小鼠同种异体移植模型中使用针对CXCR3配体Mig的中和抗体已证明CXCR3在协调T细胞介导的组织排斥反应中的重要性。
