Farivar Alexander S, Mackinnon-Patterson Brendan C, McCourtie Anton S, Ward Peter A, Mulligan Michael S
Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356310, Seattle, WA 98195, USA.
Exp Mol Pathol. 2005 Jun;78(3):171-6. doi: 10.1016/j.yexmp.2005.01.002. Epub 2005 Mar 23.
Acute cellular rejection is due in part to an upregulation of chemokine genes, resulting in eventual cell-mediated cytotoxicity. The role of chemokines in acute cardiac allograft rejection is not fully characterized presently. These studies compared the patterns of expression for multiple chemokines in rodent cardiac allograft rejection. Allogeneic transplants were performed from Brown-Norway donors to Lewis recipients. Survival studies utilized daily administration of neutralizing antisera to MCP-1, CINC, and MIP-1alpha. Patterns of mRNA and protein expression were determined by Northern blots and immunohistochemistry. Allogeneic controls rejected at mean of 6.5 days. Neutralization of MCP-1 (10.8 days, P<0.001) and MIP-1alpha (7.5 days, P=0.004) function, but not CINC (6.2 days, P>0.05), significantly prolonged allograft survival. Message expression for the beta chemokines studied were increased by day 2 and continued to increase until day 6 just before rejection, while CINC levels did not change as dramatically after day 2. Chemokine protein levels mirrored mRNA patterns by IHC analysis. MCP-1 and MIP-1alpha appear to play regulatory roles in cardiac allograft rejection, while CINC is expressed, but not functional, in injury development. Beta chemokine activity should be studied further in hope of developing more targeted immunosuppression, or identifying specific chemokines that may be useful for immunosurveillance purposes.
急性细胞排斥反应部分归因于趋化因子基因上调，最终导致细胞介导的细胞毒性。目前趋化因子在急性心脏移植排斥反应中的作用尚未完全明确。这些研究比较了啮齿动物心脏移植排斥反应中多种趋化因子的表达模式。将来自布朗-挪威供体的异体移植物移植到刘易斯受体体内。生存研究采用每日给予针对MCP-1、CINC和MIP-1α的中和抗血清。通过Northern印迹法和免疫组织化学确定mRNA和蛋白质的表达模式。异体对照的平均排斥时间为6.5天。中和MCP-1（10.8天，P<0.001）和MIP-1α（7.5天，P=0.004）的功能可显著延长移植物存活时间，但中和CINC（6.2天，P>0.05）则不能。所研究的β趋化因子的信使表达在第2天增加，并持续增加至排斥前的第6天，而CINC水平在第2天后变化不明显。通过免疫组织化学分析，趋化因子蛋白水平反映了mRNA模式。MCP-1和MIP-1α似乎在心脏移植排斥反应中起调节作用，而CINC虽有表达，但在损伤发展过程中无功能。应进一步研究β趋化因子的活性，以期开发更具针对性的免疫抑制方法，或鉴定出可能用于免疫监测目的的特定趋化因子。
