Rüster M, Sperschneider H, Fünfstück R, Stein G, Gröne H J
Department of Internal Medicine II, Friedrich Schiller University, Jena, Germany.
Clin Nephrol. 2004 Jan;61(1):30-9. doi: 10.5414/cnp61030.
The beta-chemokines MCP-1 (CCL2) and RANTES (CCL5) have been shown to play important roles in acute renal transplant rejection (AR) and chronic allograft nephropathy (CAN). The potential relationship of expression of these chemokines, their chemokine receptors CCR1, CCR2, CCR5, and the cell populations of inflammatory infiltrate, histological and clinical diagnoses were investigated in biopsies at the time of AR and compared with biopsies of CAN.
In 24 renal transplant biopsies with AR (n = 15) and CAN (n = 9), the expression of MCP-1 and RANTES, their receptors CCR1, CCR2, and CCR5 and the infiltration with monocytes/macrophages and T cells were studied.
As previously described, chemokine and chemokine receptor expression was found mainly in mononuclear cells infiltrating the interstitium and glomeruli. In the tubulointerstitial area and glomeruli the expression of MCP-1, RANTES, and their receptors correlated with an infiltration by monocytes/macrophages. Biopsies with CAN revealed a lower expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in tubulointerstitial cells, and a significantly lower infiltration with MRP14-positive monocytes/macrophages than biopsies with AR. In AR, MCP-1 and CCR1 showed a lower expression compared to RANTES, CCR2, and CCR5.
The positive correlation between chemokines and chemokine receptors and infiltrating leukocytes during acute rejection, the lower but detectable expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in CAN, and the differences in the quantity of expression between the different chemokines and chemokine receptors point to a complex regulation of chemokine expression in renal allografts. Since chemokines are not only involved in inflammation but also in tissue regeneration, this could have impact on the development of CAN.
β-趋化因子单核细胞趋化蛋白-1（MCP-1，即CCL2）和调节激活正常T细胞表达和分泌的因子（RANTES，即CCL5）已被证明在急性肾移植排斥反应（AR）和慢性移植肾肾病（CAN）中发挥重要作用。本研究调查了这些趋化因子及其趋化因子受体CCR1、CCR2、CCR5的表达与炎症浸润细胞群、组织学及临床诊断之间的潜在关系，并在AR发生时对活检组织进行研究，同时与CAN的活检组织进行比较。
对24例肾移植活检组织进行研究，其中AR组15例，CAN组9例，研究MCP-1和RANTES及其受体CCR1、CCR2和CCR5的表达，以及单核细胞/巨噬细胞和T细胞的浸润情况。
如先前所述，趋化因子和趋化因子受体表达主要见于浸润间质和肾小球的单核细胞。在肾小管间质区域和肾小球中，MCP-1、RANTES及其受体的表达与单核细胞/巨噬细胞浸润相关。CAN活检组织显示，肾小管间质细胞中MCP-1、RANTES、CCR1、CCR2和CCR5的表达较低，且MRP14阳性单核细胞/巨噬细胞浸润明显低于AR活检组织。在AR中，与RANTES、CCR2和CCR5相比，MCP-1和CCR1表达较低。
急性排斥反应期间趋化因子和趋化因子受体与浸润白细胞之间呈正相关，CAN中MCP-1、RANTES、CCR1、CCR2和CCR5表达较低但仍可检测到，且不同趋化因子和趋化因子受体的表达量存在差异，这表明肾移植中趋化因子表达存在复杂调控。由于趋化因子不仅参与炎症反应，还参与组织再生，这可能对CAN的发生发展产生影响。
