Effects of naturin 2 on colony formation by hematopoietic progenitor cells in human umbilical cord blood mediated by induction of release of growth factors.

Naturin 2, a health drink, contains a mixture of Chinese herb plants and is a potent immunomodulator. It has anti-tumor effects mediated by immune system. In the present study, low density (LD) and purified CD34+ cells (enriched for hematopoietic stem [HSC] and progenitor [HPC]) from human umbilical cord blood (CB) were assayed for colony formation in response to Naturin 2. First, we examined the in vitro activity of Naturin 2 on HPC. Naturin 2 by itself stimulated colony formation derived from either LD or CD34+ CB cells. The stimulatory effect by Naturin 2 was mediated by both direct and indirect action on HSCs/HPCs. The indirect action is via releasing of cytokines in the 5 day-conditioned media by LD CB cells with Naturin 2. The stimulatory activities in the 5 day-conditioned media (CM) could be blocked by the neutralization antibodies against interleukin (IL)-3, granulocyte macrophage (GM)-colony stimulating factor (CSF), IL-1 alpha, IL-1 beta and M-CSF. Therefore, the stimulatory activities detected in the media conditioned are due to the cytokines released in the cultures. In addition, we have also determined that addition of Naturin 2 to the cultures with LD or CD34+ cells stimulated by IL-3 and/or GM-CSF resulted in a decrease of colony formation. The inhibitory effect of Naturin 2 was mediated, at least in part, by releasing suppressive cytokines, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, in the 3 day--CM, since antibodies against these two suppressive cytokines partially blocked the inhibitory activity. These results demonstrate that Naturin 2 has differential effects on hematopoiesis.