Activity of acetyl-Ser-Asp-Lys-Pro (AcSDKP) on human hematopoietic progenitor cells in short-term and long-term bone marrow cultures

The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a potent inhibitor of h ematopoietic stem cell proliferation. We examined the effects of AcSDKP on the production of granulocyte-macrophage colony-forming cells (CFU-GM) and high proliferative potential colony-forming cells (HPP-CFC) in human long-t erm bone marrow (LTBM) cultures and CFU-GM and erythroid burst-forming cell s (BFU-e) in short-term liquid cultures. The addition of AcSDKP in short-te rm bone marrow cultures resulted in a maximum depression of the total numbe r of progenitor cells as well as the number of progenitor cells entering ce ll cycle following culture with 10(-12) to 10(-14) M AcSDKP and 10(-14) M A cSDKP when exogenous cytokines (GM-CSF, IL-3, or SCF) were added. AcSDKP wa s added daily to LTBM cultures at various concentrations (10(-8) M to 10(-1 6) M) for up to 5 weeks. In these LTBM culture studies, AcSDKP inhibited th e entry of nonadherent progenitor cells into S phase and decreased the numb er of nonadherent progenitor cells with peak activity at 10(-12) M. In cont rast, AcSDKP had no effect on the number of adherent CPU-GM, HPP-CFC, or ce llularity per culture or percent of adherent progenitor cells in S phase. T hese studies indicate that the concentration of the tetrapeptide is critica l to the activity of AcSDKP on human hematopoietic progenitor cells. Furthe rmore, we report that the presence of cytokines or stromal cells also affec ts the response of progenitor cells to AcSDKP. These results will aid in de termining kinetic properties of AcSDKP for the development of clinical prot ocols to protect normal human hematopoietic stem and progenitor cells follo wing cycle-specific chemotherapy agents.