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Direct and reversible inhibitory effect of the tetrapeptide acetyl-N-
Ser-Asp-Lys-Pro (Seraspenide) on the growth of human CD34+ subpopulations
in response to growth factors
D Bonnet, FM Lemoine, S Pontvert-Delucq, C Baillou, A Najman and M Guigon
Department of Hematology, CHU St Antoine, Paris, France.
The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP, Seraspenide; Ipsen-
Biotech, Paris, France), an inhibitor of murine spleen colony-forming units
reduces the number and the percentage in DNA synthesis of progenitors from
human unfractionated bone marrow. To determine whether AcSDKP may directly
affect the growth potential of purified progenitors even at the most
primitive level, CD34+HLA-DRhigh and CD34++HLA-DRlow cells were highly
purified by cell sorting. Then, CD34+ subsets were stimulated in liquid
culture with combinations of growth factors (GFs) and AcSDKP was added for
20 hours or 6 days and cells plated in methylcellulose. After a 20-hour
incubation, we show that AcSDKP (at 10(-10) mol/L) significantly inhibits
the colony formation of both CD34+ subsets. Moreover, when added daily for
6 days, AcSDKP: (1) reduces the proliferation of both CD34+ cell fractions
stimulated by 3 or 7 GFs, and (2) decreases the number of progenitors
generated from the CD34+HLA-DRhigh and CD34++HLA-DRlow cell fractions.
Furthermore, we show for the first time, using both high proliferative
potential cell and long-term culture initiating cell assays, that AcSDKP
inhibits the most primitive cells contained in the CD34++HLA-DRlow
subpopulation. Finally, by using limiting dilution assays we demonstrated
that AcSDKP acts directly at a single cell level and that its inhibitory
effect is reversible and dose dependent.
Volume 82,
Issue 11,
pp. 3307-3314,
12/01/1993
Copyright © 1993 by The American Society of Hematology
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