Abstract
Immunosuppressants cyclosporin A (CsA), FK506, and KM2210 modulated colony formations of murine hematopoietic progenitor cells. In a 4-h treatment with CsA, 10 μg/ml increased the formation of colony-forming units of mixed lineages (CFU-Mix) but decreased the formation of highly proliferative potential colony-forming units (CFU-HPP); 1 μg/ml of CsA increased the formations of CFU-HPP, CFU-Mix, and colony-forming units of granulocytes/macrophages (CFU-GM); 0.1 μg of CsA increased the formation of CFU-Mix and burst-forming units of erythroid lineage (BFU-E). Lower doses of CsA appeared to induce an increase in various colony formations. FK506 increased CFU-HPP and CFU-Mix formations at lower doses. Another immunosuppressant, KM2210, increased CFU-HPP and CFU-GM formations but decreased CFU-Mix and BFU-E formations. In a 24-h treatment, 10 μg/ml and 1 μg/ml of CsA inhibited all the colony formations, but 0.1 μg/ml of CsA increased CFU-Mix, CFU-GM, and BFU-E formations. Similarly, 100 ng/ml and 10 ng/ml of FK506 decreased all the colony formations but 1 ng/ml of FK506 increased CFU-HPP and CFU-GM formations. KM2210 inhibited all the colony formations. These findings showed that lower doses of CsA and FK506 appeared to increase the colony formations, although higher doses of these drugs decreased the colony formations, similar to the findings in a 4-h treatment. On the other hand, KM2210 showed opposing effects on colony formation with 4-h and 24-h treatments.
Similar content being viewed by others
References
Wang SC, Morel PA, Wang Q, Jordan ML, Simmons RL, Tweardy DJ (1993) A dual mechanism of immunosuppression by FK506. Differential suppression of IL-4 and IL-10 levels in T helper 2 cells. Transplantation 56:978–985
Nelson PA, Kawamura A, Akselband Y, Peattie DA, Aldape RA, Harding MW (1991) Effect of immunosuppressive drugs on cytokine gene transcription phenotyping (MAPPing) polymerase chain reaction. Transplant Proc 23:2867–2869
Clipstone NA, Crabtree GR (1992) Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 357:695–697
Liu J (1993) FK506 and cyclosporin, molecular probes for studying intracellular signal transduction. Immunol Today 14:290–295
Kalechman Y, Sredni B, Capsi RR, Nussenblatt RB (1990) Enhancing effect of cyclosporins A and G on bone marrow colony formation. Exp Hematol 18:1104–1107
Hirao A, Kawano Y, Takaue Y (1993) Effects of immunosuppressants, FK506, deoxyspergualin, and cyclosporin A on immature human hematopoiesis. Blood 81:1179–1183
Matsudaira T, Kodo H, Okamoto S-I, Tani K, Tojo A, Ozawa K, Asano K, Asano S (1992) The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice. Transplantation 54:676–681
Imamura M, Han M, Hashino S, Kobayashi H, Imai K, Kobayashi S, Tanaka J, Zhu X, Kobayashi M, Fujii Y, Kasai M, Sakurada K, Miyazaki T (1994) In vivo effects of the immunosuppressant 15-deoxyspergualin on hematopoiesis in murine allogeneic bone marrow chimeras: its thrombopoietic activity and reversal of adverse effects with granulocyte colonystimulating factor and/or erythropoietin. Transplantation 58:214–223
Zhu X, Imamura M, Tanaka J, Han CW, Hashino S, Imai K, Asano M, Nakane A, Minagawa T, Kobayashi M, Sakurada K, Miyazaki T (1994) Effects of 15-deoxyspergualin in vitro and in vivo on cytokine gene expression. Transplantation 58:1104–1109
Han C-W, Imamura M, Hashino S, Zhu X, Tanaka J, Imai K, Matsudaira T, Asano S (1995) Differential effects of the immunosuppressants cyclosporin A, FK506 and KM2210 on cytokine gene expression. Bone Marrow Transplant 15:733–739
Bradley TR, Hodgson GS (1979) Detection of primitive macrophage progenitor cells in mouse bone marrow. Blood 54:1446–1450
Liu J, Farmer JDJr, Lane WS, Friedman J, Weissman I, Schreiber SL (1991) Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66:807–815
Friedman J, Weissman I (1991) Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: one in the presence and one in the abscence of CsA. Cell 66:799–806
Braun W, Kallen J, Mikol V, Walkinshaw MD, Wuthrich K (1995) Three-dimensional structure and actions of immunosuppressants and their immunophilins. FASEB J 9:63–72
Yoshimura N, Matsui S, Hamashima T, Oka T (1989) Effect of a new immunisuppressive agent, FK506, on human lymphocyte responses in vitro. I. FK506 inhibits the expression of alloantigen-activated suppressor cells as well as the induction of alloreactivity. Transplantation 47:351–356
Han C-W, Imamura M, Zhu X, Tanaka J, Hashino S, Asaka M, Matsudaira T, Asano S (1995) Modulation of cytokine gene expression in unstimulated bone marrow and spleen cells treated with immunosuppressants FK506 and KM2210. Immunobiology (in press)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zhu, X., Imamura, M., Hashino, S. et al. Enhancing and suppressive effects of immunosuppressants cyclosporin A, FK506, and KM2210 on the colony formation of murine bone marrow cells. Ann Hematol 71, 301–306 (1995). https://doi.org/10.1007/BF01697983
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01697983