The impaired ability of human monocytes to stimulate autologous and allogeneic mixed lymphocyte reactions after exposure to cyclosporine. Associated alterations of HLA-DR expression and physical characteristics of monocytes.
Human monocytes (M phi) preexposed to cyclosporine (CsA) concentrations ranging between 1.0 and 10.0 micrograms/ml were impaired in their ability to stimulate autologous and allogeneic mixed lymphocyte reactions (MLR) when they were compared with control M phi unexposed to CsA. M phi preexposed to CsA and M phi preexposed to PGE2 displayed reduced expression of HLA-DR. Indomethacin protected M phi from decreased HLA-DR expression at lower CsA concentrations, but was unable to prevent the decrease of HLA-DR with higher concentrations of CsA. CsA appeared capable of perturbing M phi membranes because decreases in the indirect light scattering properties of M phi were detected with the various CsA concentrations tested. Higher CsA concentrations significantly reduced the cellular volumes of M phi. The reductions of cellular volume were considerably less than the decreases in indirect light scatter. These data show that CsA interacts directly with M phi, reducing their functional ability to trigger MLR responses and their phenotypic expression of HLA-DR. The decreased HLA-DR expression is mediated via prostaglandins at low CsA concentrations and the decreased HLA-DR expression is mediated via membrane perturbations unrelated to prostaglandins at high CsA concentrations.
Whisler
R L
RL
Lindsey
J A
JA
Proctor
K V
KV
Newhouse
Y G
YG
Cornwell
D G
DG
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology*; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D003524:Cyclosporins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II