Thymosin beta4, inhibitor for normal hematopoietic progenitor cells.
Thymosin beta4 (Tbeta4), isolated from the calf thymus fraction 5, has a ubiquitous localization and plays a pleiotropic role in both the immune and nonimmune systems. Because it contains at its N-terminal end the sequence of a known inhibitor of hematopoiesis, the acetylated tetrapeptide Ac-N-Ser-Asp-Lys-Pro (AcSDKP, Goralatide), we have assayed Tbeta4 on human hematopoietic cells. We demonstrate that it inhibits normal bone marrow progenitor cell growth; indeed, it decreased the growth of both granulo-macrophagic and erythroid progenitors and reduces their percentage in S phase. Furthermore, we show that Tbeta4 reduces both the clonogenicity and the cell proliferation of purified CD34+ cells induced by a combination of seven growth factors. Although Tbeta4's inhibitory effect is very similar to that of AcSDKP, we demonstrate, using neutralizing antibodies and a truncated form of Tbeta4 devoid of the AcSDKP sequence, that the inhibitory effect of Tbeta4 is not mediated by the sequence AcSDKP. These data indicate that Tbeta4 is a novel inhibitor for human normal hematopoietic progenitors.
Bonnet
D
D
Department of Hematology, CHU Saint Antoine, Paris, France.
Lemoine
F M
FM
Frobert
Y
Y
Bonnet
M L
ML
Baillou
C
C
Najman
A
A
Guigon
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013947:Thymosin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D000099201:Thymosin beta(4)
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D016298:Hematopoietic Cell Growth Factors; D009842:Oligopeptides; D011994:Recombinant Proteins; D013947:Thymosin; D000099201:Thymosin beta(4); C058504:goralatide