Solomon Michelle F, Kuziel William A, Simeonovic Charmaine J
Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University, G.P.O. Box 334, Canberra, A.C.T 2601, Australia.
Cell Transplant. 2004;13(5):503-14. doi: 10.3727/000000004783983611.
Chemokines regulate the recruitment of leukocytes to sites of inflammation and may therefore play an important role in lymphocyte trafficking between draining lymph nodes and pancreatic islet tissue allografts. The intragraft expression of alpha- and beta-chemokine mRNA during the rejection of BALB/c proislet (fetal precursor islet tissue) allografts in CBA/H mice was assessed quantitatively and semiquantitatively by RT-PCR analyses. Allograft rejection was associated with the strongly enhanced (from day 4) and prolonged expression (up to day 10) of the alpha-chemokine IP-10 and enhanced intragraft mRNA expression of the beta-chemokines MCP-1, MIP-lalpha, MIP-1beta, RANTES, and eotaxin. Peak transcript expression was identified at day 4 (IP-10, MCP-1), day 5 (eotaxin), day 6 (MIP-1alpha, MIP-1beta), and day 14 (RANTES). To examine the role of beta-chemokine receptors in allograft rejection, additional allografts to CCR2-/- , CCR5-/-, and wild-type CCR+/+ mice were analyzed by histology, immunohistochemistry, and morphometry. In CCR5-/- mice, the intragraft recruitment of T cells and macrophages was slower and allograft destruction was delayed; in CCR2-/- mice, the initial entry of macrophages was retarded but graft survival was not prolonged. These findings suggest that IP-10 regulates the initial influx of T cells into proislet allografts, MCP-1/CCR2 signaling controls initial macrophage entry, and the MIP-1alpha, MIP-1beta, and RANTES/CCR5 pathway contributes to the rejection response by subsequently amplifying the recruitment of T cell subpopulations required for graft destruction.
趋化因子调节白细胞向炎症部位的募集，因此可能在引流淋巴结和胰岛组织同种异体移植物之间的淋巴细胞运输中发挥重要作用。通过逆转录聚合酶链反应（RT-PCR）分析，对CBA/H小鼠体内BALB/c胰岛前体细胞（胎儿胰岛前体组织）同种异体移植排斥反应期间α和β趋化因子mRNA的移植内表达进行了定量和半定量评估。同种异体移植排斥反应与α趋化因子IP-10的强烈增强表达（从第4天开始）和持续表达（直至第10天）以及β趋化因子MCP-1、MIP-1α、MIP-1β、RANTES和嗜酸性粒细胞趋化因子的移植内mRNA表达增强相关。在第4天（IP-10、MCP-1）、第5天（嗜酸性粒细胞趋化因子）、第6天（MIP-1α、MIP-1β）和第14天（RANTES）鉴定到转录本表达峰值。为了研究β趋化因子受体在同种异体移植排斥反应中的作用，通过组织学、免疫组织化学和形态测量学对CCR2-/-、CCR5-/-和野生型CCR+/+小鼠的额外同种异体移植进行了分析。在CCR5-/-小鼠中，T细胞和巨噬细胞的移植内募集较慢，同种异体移植破坏延迟；在CCR2-/-小鼠中，巨噬细胞的初始进入受阻，但移植物存活时间未延长。这些发现表明，IP-10调节T细胞向胰岛前体同种异体移植物的初始流入，MCP-1/CCR2信号控制巨噬细胞的初始进入，而MIP-1α、MIP-1β和RANTES/CCR5途径通过随后放大移植物破坏所需的T细胞亚群的募集，促进排斥反应。
