Roth J, Goebeler M, Erpenstein U, Sorg C
Institute of Experimental Dermatology, University of Münster, Germany.
Transplantation. 1994 Jan;57(1):127-33. doi: 10.1097/00007890-199401000-00020.
CsA, AZA, and dexamethasone (DEX) were examined for their ability to modulate expression of surface antigens on human monocytes. Peripheral blood monocytes were cultured for 1 day, treated with various concentrations of immunosuppressants, and subsequently analyzed for expression of macrophage differentiation antigen RM3/1, intercellular adhesion molecule-1 (CD54), beta 2-integrin (CD18), and HLA-DR using flow cytometry and indirect immunofluorescence microscopy. The RM3/1 antigen was found to be significantly down-regulated by CsA and AZA in a dose-dependent manner, whereas DEX led to a marked up-regulation of the RM3/1 molecule. In contrast, expression of CD54, CD18, and HLA-DR by macrophages was not affected by treatment with these immunosuppressants. Effects of AZA, CsA, and DEX on RM3/1 surface expression were shown to be mediated via modulation of RM3/1 de novo synthesis. Immunohistochemical analysis of rejected renal allografts revealed that the RM3/1 antigen is expressed by the majority of infiltrating macrophages. Our data demonstrate that CsA, AZA, and DEX differentially affect gene expression, resulting in distinct macrophage phenotypes. Characterization of the RM3/1+ macrophage population in vitro and during the course of allograft rejection in vivo may thus provide further insights regarding the mode of immunosuppressant action on nonspecific effector mechanisms.
研究了环孢素A（CsA）、硫唑嘌呤（AZA）和地塞米松（DEX）调节人类单核细胞表面抗原表达的能力。外周血单核细胞培养1天，用不同浓度的免疫抑制剂处理，随后使用流式细胞术和间接免疫荧光显微镜分析巨噬细胞分化抗原RM3/1、细胞间黏附分子-1（CD54）、β2整合素（CD18）和人类白细胞抗原DR（HLA-DR）的表达。发现CsA和AZA以剂量依赖性方式显著下调RM3/1抗原，而DEX导致RM3/1分子明显上调。相比之下，巨噬细胞的CD54、CD18和HLA-DR表达不受这些免疫抑制剂处理的影响。结果表明，AZA、CsA和DEX对RM3/1表面表达的影响是通过调节RM3/1的从头合成介导的。对移植肾排斥反应的免疫组织化学分析显示，大多数浸润巨噬细胞表达RM3/1抗原。我们的数据表明，CsA, AZA和DEX对基因表达有不同影响，导致不同的巨噬细胞表型。因此，体外和体内同种异体移植排斥过程中RM3/1+巨噬细胞群体的特征可能为免疫抑制剂对非特异性效应机制的作用方式提供进一步的见解。
