Schröppel Bernd, Zhang Nan, Chen Peng, Zang Weiping, Chen Dongmei, Hudkins Kelly L, Kuziel William A, Sung Randall, Bromberg Jonathan S, Murphy Barbara
Division of Nephrology, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
J Am Soc Nephrol. 2004 Jul;15(7):1853-61. doi: 10.1097/01.asn.0000130622.48066.d9.
Chemokines and their receptors play a pivotal role in the initiation and amplification of the immune response. Investigated was their differential expression after syngeneic and allogeneic islet transplantation. During the 7 d after transplantation, the chemokines MCP-1, MCP-2, RANTES, MIG, IP-10, I-TAC, and two CC chemokine receptors CCR2 and CCR5 were highly expressed in allografts when compared with isografts. Disrupting the CCR2 and CCR5 pathways individually resulted in prolongation of the survival time 16.1 +/- 0.4 and 15.8 +/- 0.9 d, respectively, of fully major histocompatibility complex-mismatched islet grafts compared with wild-type controls (11.2 +/- 1.0 d). Blockade of both receptors had no synergistic effect. Rapamycin-treated wild-type recipients rejected their grafts at 17.4 +/- 2.2 d, in contrast to rapamycin-treated CCR2-/- recipients at 38 +/- 8.6 d (P = 0.025). The disruption of the CCR2 and CCR5 signaling, alone or in combination, moderately prolong islet allograft survival. However, the combination of low-dose immunosuppression and targeting of CCR2 greatly augmented islet graft survival.
趋化因子及其受体在免疫反应的启动和放大过程中发挥着关键作用。研究了它们在同基因和异基因胰岛移植后的差异表达。在移植后的7天内，与同基因移植相比，趋化因子MCP-1、MCP-2、RANTES、MIG、IP-10、I-TAC以及两种CC趋化因子受体CCR2和CCR5在异基因移植中高表达。单独破坏CCR2和CCR5通路分别使完全主要组织相容性复合体不匹配的胰岛移植的存活时间延长至16.1±0.4天和15.8±0.9天，而野生型对照为11.2±1.0天。阻断这两种受体没有协同作用。雷帕霉素处理的野生型受体在17.4±2.2天排斥其移植，而雷帕霉素处理的CCR2-/-受体在38±8.6天排斥（P = 0.025）。CCR2和CCR5信号的破坏，单独或联合使用，可适度延长胰岛移植的存活时间。然而，低剂量免疫抑制与靶向CCR2的联合使用极大地延长了胰岛移植的存活时间。
