Heemann U, Azuma H, Schmid C, Philipp T, Tilney N
Department of Nephrology, University Hospital Essen, Germany.
Clin Nephrol. 1996 May;45(5):355-7.
Mycophenolic acid mofetil (MMF) is an agent which has recently gained a lot of attention. In clinical trials MMF has reduced the rate of acute rejection episodes in human recipients of kidney allografts by inhibiting inosin-monophosphat-dehydrogenasis (IMPDH), an enzyme involved in the purin metabolism and related to the expression of adhesion molecules. The aim of the present study was to analyze the effects of MMF upon the expression of adhesion molecules in transplanted kidney allografts. LBNF1 kidneys were orthotopically transplanted into Lewis rats and either treated with MMF (20 mg/kg/day) or vehicle. Rats were harvested 3, 5 and 7 days following transplantation. Immunohistology was performed with various monoclonal antibodies. In general, MMF resulted in a better preservation of graft structure by 7 days. Cellular infiltration and tubular atrophy were less pronounced. At day 3, macrophages were diminished in MMF-treated animals to a high extent, while the number of T-cells was almost identical as compared to controls. In addition, the number of cells positive for MHC class II and LFA-1 was reduced in the MMF-treated animals. In conclusion, MMF resulted in a markedly reduced leukocyte infiltrate, presumably based on a reduced expression of lymphocytic adhesion molecules and an interaction with macrophages.
霉酚酸酯（MMF）是一种最近备受关注的药物。在临床试验中，MMF通过抑制肌苷单磷酸脱氢酶（IMPDH）降低了肾移植受者急性排斥反应的发生率，IMPDH是一种参与嘌呤代谢且与黏附分子表达相关的酶。本研究的目的是分析MMF对移植肾同种异体移植物中黏附分子表达的影响。将LBNF1肾原位移植到Lewis大鼠体内，并分别用MMF（20mg/kg/天）或赋形剂处理。移植后3、5和7天处死大鼠。用各种单克隆抗体进行免疫组织学检查。总体而言，到第7天时MMF能更好地保存移植物结构。细胞浸润和肾小管萎缩不太明显。在第3天，接受MMF治疗的动物体内巨噬细胞数量大幅减少，而T细胞数量与对照组几乎相同。此外，接受MMF治疗的动物体内MHC II类和淋巴细胞功能相关抗原-1（LFA-1）阳性细胞数量减少。总之，MMF导致白细胞浸润明显减少，这可能是基于淋巴细胞黏附分子表达降低以及与巨噬细胞的相互作用。
