ENHANCING AND SUPPRESSIVE EFFECTS OF IMMUNOSUPPRESSANTS CYCLOSPORINE-A, FK506, AND KM2210 ON THE COLONY FORMATION OF MURINE BONE-MARROW CELLS

Immunosuppressants cyclosporin A (CsA), FK506, and KM2210 modulated co lony formations of murine hematopoietic progenitor cells. In a 4-h tre atment with CsA, 10 mu g/ml increased the formation of colony-forming units of mixed lineages (CFU-Mix) but decreased the formation of highl y proliferative potential colony-forming units (CFU-HPP); 1 mu g/ml of CsA increased the formations of CFU-HPP, CFU-Mix, and colony-forming units of granulocytes/macrophages (CFU-GM); 0.1 mu g 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 l ower doses. Another immunosuppressant, KM2210, CFU-HPP and CFU-GM form ations but CFU-Mix and BFU-E formations. In a 24-h treatment, 10 mu g/ ml and 1 mu g/ml of CsA inhibited all the colony formations, but 0.1 m u g/ml of CsA increased CFU-Mix, CFU-GM, and BFU-E formations. Similar ly, 100 ng/ml and 10 ng/ml of FK506 decreased all the colony formation s 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, al though higher doses of these drugs decreased the colony formations, si milar to the findings in a 4-h treatment. On the other hand, KM2210 sh owed opposing effects on colony formation with 4-h and 24-h treatments .