病毒巨噬细胞炎性蛋白与趋化因子受体结合的效应分析  

Biological functions of binding of viral macrophage inflammatory protein to chemokine receptor

作　　者：杨清玲[1] 丁勇兴[2] 张玉心[1] 连超群[1] 

机构地区：[1]蚌埠医学院生物化学与分子生物学教研室,安徽蚌埠233030 [2]安徽省蚌埠市第三人民医院普外肿瘤科,安徽蚌埠233000

出　　处：《蚌埠医学院学报》2006年第3期226-229,共4页Journal of Bengbu Medical College

基　　金：安徽省教育厅自然科学研究资助项目(2005kj374zc);安徽省高校青年教师科研计划资助(2005jq1121)

摘　　要：目的:探讨人疱疹病毒8 K6基因编码的产物病毒巨噬细胞炎性蛋白(viral m acrophage inflamm atory prote in,vM IP)是否具有结合趋化因子受体以及趋化作用。方法:受体配体交联试验检测vM IP与受体结合能力。趋化实验及细胞内钙流检测判断vM IP的生物学活性。结果:vM IP可与外周血单个核细胞(PBMCs)膜上的趋化因子受体结合,抑制hM IP-1α对PBMC的趋化能力,EC50为3.39 ng/m l。其本身只有较弱的趋化能力。钙流实验证实vM IP轻度升高胞内钙离子浓度,但可明显抑制hM IP-1α所引起的胞内钙离子高峰。结论:重组vM IP与hM IP-1α受体(CCR5)结合后,可有效的阻断人源性趋化因子的结合与信号传导,但其本身对细胞未有明显的激活作用,因此可作为趋化因子受体的天然阻断剂,可用于免疫移植中的排斥反应或H IV-1病毒感染等。Objective：To explore the biological activities of viral macrophage inflammatory protein （vMIP） encoded by K6 gene of human herpesvirus 8. Methods： Combined ability of vMIP to receptors was measured by Cross-linking assays. Biological activity of vMIP were measured with Cellular chemotaxis assays and calcium mobilization. Results ： Cross-linking assays showed that vMIP bound with receptors of peripheral blood mononuclear, and vMIP suppressed by chemotacitic activity of PBMCs to human macrophage inflammatory protein （hMIP-1 α） and EC50 = 3.39 ng/ml. But itself was not remarkably associated with the normal, rapid mobilization of calcium from intracellnlar stores. Instead,it blocked calcium mobilization induced by endogenous chemokines. Conclusions：The study has demonstrated that vMIP can bind to receptor of hMIP-1 （CCRS） and stop it from hMIP-1 and conduction of messages. But itself did not induce cellular chemotaxis,meaning that vMIP has ability of binding to CCR5 similar hMIP-1 α and absent of function activating receptor llke hMIP-1α,so vMIP only has sealing effect on CCRS. This also suggests that only of effects of vMIP is to seal CCR5 of host cells,vMIP is the natural scaling factor for CCR5 and result in inhibiting inflammatory reaction mediated by interaction between CCR5 and human MIPs, so possibly it is important value in prevention and treatment of inflammation, transplantion immunity and HIV infection.

关 键 词：趋化因子 巨噬细胞 病毒巨噬细胞炎性蛋白 趋化因子受体 趋化实验 钙流 

分 类 号：R392.12[医药卫生—免疫学]