Journal of Leukocyte Biology BioLegend: Treg, Th17, Stem Cell
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(Journal of Leukocyte Biology. 2003;73:297-305.)
© 2003 by Society for Leukocyte Biology

The improved survival of hematopoietic cells cultured with a fusion protein of insulin-like growth factor II (IGF-II) and interleukin 3 (IL-3) is associated with increases in Bcl-xL and phosphatidylinositol-3 kinase activity

Marcos R. DiFalco*,{dagger},{ddagger}, Suhad Ali*,§ and Luis Fernando Congote*,{dagger},{ddagger}

* Departments of Medicine and
{dagger} Biochemistry, McGill University, and
{ddagger} Endocrine Laboratory and
§ Division of Hematology, McGill University Health Centre, Montreal, Canada

Correspondence: L. F. Congote, McGill University Health Centre, Endocrine Laboratory, 687 Avenue des Pins, Ouest, Montreal, Canada H3A 1A1. E-mail: luis.f.congote{at}muhc.mcgill.ca

We compared the antiapoptotic activity of a recombinant chimera of insulin-like growth factor II (IGF-II) and interleukin (IL)-3 with the corresponding equimolar mixture of the individual components based on changes in several factors associated with survival in the CD34+ human hematopoietic cell line TF-1. Propidium iodide-stained cells analyzed by fluorescein-activated cell sorter indicated that the chimera was more effective than the corresponding equimolar mixture in decreasing the amounts of apoptotic cells and increasing the proportion of cells in the S-phase of the cell cycle. The chimera was more effective in increasing the antiapoptotic protein BclxL and produced a significant increase in signal transducer and activator of transcription-5 phosphorylation and in phosphatidylinositol-3 kinase (PI-3K) activity. The PI-3K inhibitor LY294002 specifically inhibited cell survival in the presence of the chimera, suggesting a key role of this enzyme in the potentiation of survival caused by the linkage of IGF and IL-3. This potentiation of survival and its preferential inhibition by LY294002 were also observed in a nontransformed, primary culture of human umbilical cord endothelial cells.

Key Words: Stat5 • CD34







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