Organ-specific differences in the function of MCP-1 and CXCR3 during cardiac and skin allograft rejection
Organ-specific differences in the function of MCP-1 and CXCR3 during cardiac and skin allograft rejection
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DOI：
10.1097/01.tp.0000266892.69117.9a
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发表时间：
2007-06-27
期刊：
影响因子：
6.2
通讯作者：
Briscoe, David M.
中科院分区：
文献类型：
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作者：
Haskova, Zdenka;Izawa, Atsushi;Briscoe, David M.
背景资料。趋化因子在排斥反应过程中将白细胞募集到同种异体移植物中是公认的作用。此外，一些研究表明，趋化因子的功能存在器官特异性差异，但这种差异的机制尚不清楚。以BALB/c(H-2(D))、C5713L/6(H-2(B))、MCP-1(-/-)(H-2(B))和CXCR3(-/-)(H-2(B))小鼠为供体或受体，进行完全主要组织相容性复合体不匹配的带血管心脏移植或皮肤移植。此外，在移植时或28天后，将H-2(B)皮肤移植到接受BALB/c脾细胞(H-2(D))的SCID小鼠(H-2(D))上。单核细胞趋化蛋白-1(-/-)受者的同种异体心脏移植存活时间显著长于野生型(WT)对照组(P<；0.0005)。然而，在WT小鼠中，使用MCP-1(-/-)移植物作为供体并不能延长存活时间。相反，供体而不是受体MCP-I的缺失延长了同种异体皮肤移植的存活时间。CXCR3(-/-)受者的供心移植存活时间略有延长(P<；0.0005)，而WT受者的CXCR3(-/-)供心的排斥反应与对照组相似。此外，虽然受体CXCR3对皮肤排斥反应没有影响，但CXCR3(-/-)供体皮肤移植物的存活时间明显长于WT对照组。在SCID排斥反应模型中，使用带血管的CXCR3(-/-)皮肤移植物作为供体时，这种生存优势消失了。受体来源的MCP-1和CXCR3在血管化同种异体移植物的排斥反应中起作用，但不是非血管化同种异体移植物的排斥反应。相反，供者来源的MCP-1和CXCR3在非血管化的移植物中具有功能，但不能用于血管化的移植物。
Background. Chemokines are well-established to function in, the recruitment of leukocytes into allografts in the course of rejection. Moreover, some studies have indicated that there are organ-specific differences in chemokine function, but the mechanism accounting for this difference is not known.Methods. Fully major histocompatibility complex-mismatched vascularized cardiac transplants or skin transplants were performed using BALB/c (H-2(d)), C5713L/6 (H-2(b)), MCP-1(-/-) (H-2(b)) and CXCR3(-/-) (H-2(b)) mice as donors or recipients. Also, skin grafts (H-2(b)) were placed onto SCID mice (H-2(d)) that received BALB/c splenocytes (H-2(d)) by adoptive transfer either at the time of transplantation, or after a period of 28 days.Results. Cardiac allografts in MCP-1(-/-) recipients survived significantly longer (P < 0.0005) than wild-type (WT) controls. However, there was no prolongation of survival when MCP-1(-/-) grafts were used a donors in WT mice. In contrast, the absence of donor but not recipient MCP- I prolonged skin allograft survival. WT donor cardiac grafts in CXCR3(-/-) recipients had a modest prolongation of survival (P < 0.0005), whereas CXCR3(-/-) donor cardiac grafts in WT recipients were rejected similar to controls. Also, while recipient CXCR3 had no effect on the rejection of skin, CXCR3(-/-) donor skin grafts survived significantly longer than WT controls. This survival advantage was lost when vascularized CXCR3(-/-) skin grafts were used as donors in the SCID model of rejection.Conclusion. Recipient derived MCP-1 and CXCR3 are functional in the rejection of vascularized, but not nonvascularized, allografts. In contrast, donor-derived MCP-1 and CXCR3 are functional in nonvascularized, but not vascularized grafts.