Activity of some natural and modified (fluorescent) cyclosporins on T cells.
A simple test system for comparing the proliferation inhibition properties of cyclosporins (Cs) on susceptible T cells is described. This test was applied to a number of natural and chemically altered Cs-compounds, the latter from inactive, hypo-active and hyper-active Cs. These cyclosporins constituted standards for further comparison of the activities of new Cs such as fluorescent derivatives of the molecules, and especially for determining their mechanism of action. The use of Cs-sensitive (CsS) and Cs-resistant (CsR) cell lines permitted the distinction between specific cytostatic and generalized cytotoxic effects. Active--but not inactive--Cs were found to cause the appearance of refractive globular bodies in both CsS and CrR lymphocytes and in macrophages. When active fluorescent Cs were used, Cs detectable by fluorescence after one or several days was found to be concentrated within these globular bodies.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002999:Clone Cells / Q000276:immunology; D003524:Cyclosporins / Q000378:metabolism / Q000494:pharmacology*; D003619:Dansyl Compounds / Q000378:metabolism / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D002479:Inclusion Bodies / Q000032:analysis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000032:analysis / Q000187:drug effects; D051379:Mice; D008806:Mice, Inbred AKR; D051381:Rats; D013601:T-Lymphocytes / Q000032:analysis / Q000187:drug effects / Q000276:immunology*
D000954:Antigens, Surface; D003524:Cyclosporins; D003619:Dansyl Compounds; D007166:Immunosuppressive Agents; C016338:dansyl fluoride