Walle A J, Wong G Y, Suthanthiran M, Rubin A L, Stenzel K H
Rogosin Institute, New York Hospital, New York.
Transplantation. 1988 Mar;45(3):534-6. doi: 10.1097/00007890-198803000-00006.
High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo.
给予肾移植受者大剂量类固醇以治疗急性移植排斥反应可能会影响外周血单核(PBM)细胞的细胞周期进程。在8例临床稳定期患者以及另外10例急性排斥反应发作期和大剂量类固醇给药7天期间的患者中,测量了PBM细胞的DNA合成以及细胞DNA和RNA含量。肾功能改善证明10例患者的排斥反应成功逆转。与稳定期患者相比,处于排斥反应期的患者经历克隆扩增的细胞数量更多,即G1期细胞以及增殖期或S、G2和M(SG2M)期细胞的比例更高。类固醇治疗对体内G1期或SG2M期细胞的比例或体外PBM细胞掺入3H胸腺嘧啶核苷均无急性影响。然而,在高剂量类固醇治疗7天内,细胞周期复制前区室的细胞(G0/1期细胞)的RNA含量显著降低。结果表明,类固醇不会急性影响体内经历克隆扩增的细胞的转录后合成和核酸含量。因此,肾移植受者同种异体刺激的PBM细胞的复制前期可能是体内对类固醇最敏感的细胞周期阶段。