Inhibition of human bone marrow progenitors by the synthetic tetrapeptide AcSDKP.
The purpose of this work was to study the effects of a tetrapeptide, acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of spleen colony-forming unit (CFU-S) entry into DNA synthesis, on human progenitor cells. Normal human mononuclear cells were incubated with concentrations of the synthetic tetrapeptide ranging from 10(-12) to 10(-7) M for 1.5 and 24 h and then plated in methylcellulose in the presence of human placenta-conditioned medium and recombinant human erythropoietin. The proportion of progenitors in DNA synthesis was determined by the thymidine suicide assay. Incubation with AcSDKP for 24 h leads to a significant inhibition of granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth and in some cases of erythroid colony-forming unit (CFU-E) growth. The inhibition, which was never greater than 50%, was obtained with 10(-10)-10(-9) M AcSDKP, whereas no effect was seen at higher concentrations. The percentage of CFU-GM, BFU-E, and CFU-E in DNA synthesis was significantly reduced in five consecutive patients after incubation of cells for 24 h with inhibitory doses of the peptide, indicating that it is active on cycling cells. Therefore, these studies provide the first evidence that the tetrapeptide AcSDKP, originally obtained from bovine marrow and now chemically synthesized, is able to inhibit the in vitro growth of human progenitors and to decrease their proportion in cell cycle.
Guigon
M
M
Département of Hematology, Faculté de Médecine Saint Antoine, Paris, France.
Bonnet
D
D
Lemoine
F
F
Kobari
L
L
Parmentier
C
C
Mary
J Y
JY
Najman
A
A
D000595:Amino Acid Sequence; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*
D009842:Oligopeptides; D004247:DNA; C058504:goralatide