DIFFERENTIAL REGULATION OF THE MACROPHAGE-SPECIFIC SURFACE-ANTIGEN RM3 1 BY CYCLOSPORINE, AZATHIOPRINE, AND DEXAMETHASONE/

CsA, AZA, and dexamethasone (DEX) were examined for their ability to m odulate expression of surface antigens on human monocytes. Peripheral blood monocytes were cultured for 1 day, treated with various concentr ations of immunosuppressants, and subsequently analyzed for expression of macrophage differentiation antigen RM3/1, intercellular adhesion m olecule-1 (CD54), beta(2)-integrin (CD18), and HLA-DR using flow cytom etry and indirect immunofluorescence microscopy. The RM3/1 antigen was found to be significantly downregulated by CsA and AZA in a dose-depe ndent manner, whereas DEX led to a marked up-regulation of the RM3/1 m olecule. In contrast, expression of CD54, CD18, and HLA-DR by macropha ges was not affected by treatment with these immunosuppressants. Effec ts of AZA, CsA, and DEX on RM3/1 surface expression were shown to be m ediated 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 de monstrate 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 allo graft rejection in vivo may thus provide further insights regarding th e mode of immunosuppressant action on nonspecific effector mechanisms.