Effect of cyclosporin A (CyA) on the in vitro growth of hemopoietic progenitors from normal marrow.
Unfractionated normal bone marrow cells (NBM), adherent-cell-depleted NBM, and E-rosette-depleted NBM were plated in vitro for CFU-c or BFU-E formation at plateau concentrations of colony-stimulating activity (CSA) or erythropoietin, untreated or after preincubation with cyclosporin A (CyA). At concentrations of 1000 or 2000 ng/ml, CyA enhanced CFU-c growth up to 137 +/- 32% and 147 +/- 31% of expected baseline growth respectively (p = 0.005 and 0.001). When CyA was added to NBM depleted of T cells by rosetting once with sheep red blood cells (SRBC) there was no CFU-c enhancement at CyA concentrations of 1000 ng/ml, but enhancement could be seen at 2000-5000 ng/ml. The enhancing effect of CyA was completely abolished, however, when the SRBC rosetting procedure was repeated twice (95 +/- 37% of expected growth). On the other hand, removal of adherent cells was without effect on CFU-c enhancement mediated by CyA. The addition of CyA to NBM also enhanced the growth of BFU-E (256 +/- 182% of expected growth) (p = 0.001). The results of this study suggest that CyA can increase the plating efficiency of NBM cells, possibly by inhibiting an endogenous, T-cell-mediated, suppressor mechanism.
D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007700:Kinetics
D003115:Colony-Stimulating Factors; D003524:Cyclosporins