THYMOSIN BETA-4, INHIBITOR FOR NORMAL HEMATOPOIETIC PROGENITOR CELLS

Thymosin beta 4 (T beta 4), 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 e nd the sequence of a known inhibitor of hematopoiesis, the acetylated tetrapeptide Ac-N-Ser-Asp-Lys-Pro (AcSDKP, Goralatide), we have assaye d T beta 4 on human hematopoietic cells. We demonstrate that it inhibi ts normal bone marrow progenitor fell growth; indeed, it decreases the growth of both granulo-macrophagic and erythroid progenitors and redu ces their percentage in S phase. Furthermore, we show that T beta 4 re duces both the clonogenicity and the cell proliferation of purified CD 34(+) cells induced by a combination of seven growth factors. Although T beta 4's inhibitory effect is very similar to that of AcSDKP, we de monstrate, using neutralizing antibodies and a truncated form of T bet a 4 devoid of fhf AcSDKP sequence, that the inhibitory effect of T bet a 4 is not mediated by the sequence AcSDKP. These data indicate that T beta 4 is a novel inhibitor for human normal hematopoietic progenitor s.