J. Roth et al., DIFFERENTIAL REGULATION OF THE MACROPHAGE-SPECIFIC SURFACE-ANTIGEN RM3 1 BY CYCLOSPORINE, AZATHIOPRINE, AND DEXAMETHASONE/, Transplantation, 57(1), 1994, pp. 127-133
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.