Reversible inhibitory effects and absence of toxicity of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in human long-term bone marrow culture.
The effects of acetyl-N-Ser-Asp-Lys-Pro (Ac-SDKP) in human long-term bone marrow cultures (LTBMCs) were assessed by measuring the number of progenitors and the development of stromal cells over a 6-week course. In a first set of experiments, AcSDKP was added weekly at each medium change. Under these conditions, no significant effect of the peptide was observed. In contrast, by adding AcSDKP daily at 10(-10) M, the growth of the progenitors of the non-adherent (NA) compartment was inhibited by about 35%. This inhibition was entirely reversible; after stopping the addition of the peptide at the fourth week, the number of progenitors returned to control level within 2 weeks. Conversely, AcSDKP did not significantly change the number of the progenitors present in the adherent layer. In addition, AcSDKP did not affect the formation of the stromal layer nor induce the secretion of cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3), or interleukin 6 (IL-6). Our results indicate that AcSDKP has inhibitory but reversible effects on NA progenitors and does not induce long-term modifications of the microenvironment, both of particular interest for its clinical application.
Bonnet
D
D
Department of Hematology, Faculté de Médecine Saint Antoine, Paris, France.
Lemoine
F M
FM
Khoury
E
E
Pradelles
P
P
Najman
A
A
Guigon
M
M
D000595:Amino Acid Sequence; D001853:Bone Marrow / Q000737:chemistry / Q000378:metabolism; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000032:analysis / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D007377:Interleukin-3; D015850:Interleukin-6; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; C058504:goralatide