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 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.
Roth
J
J
Institute of Experimental Dermatology, University of Münster, Germany.
Goebeler
M
M
Erpenstein
U
U
Sorg
C
C
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001379:Azathioprine / Q000494:pharmacology*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D016030:Kidney Transplantation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D003907:Dexamethasone; D016572:Cyclosporine; D001379:Azathioprine