ENDOTHELIAL-CELL SUPPORT OF HEMATOPOIESIS IS DIFFERENTIALLY ALTERED BY IL-1 AND GLUCOCORTICOIDS

We investigated the ability of endothelial cells (EC) to support hemat opoiesis in contact and Pion-contact cocultures with isolated CD34(+) or CD34(+)/CD38(low) cells. In the absence of exogenous cytokines, umb ilical vein EC (HUVEC) efficiently support proliferation of hematopoie tic cells and generation of colony-forming cells (CFC), Cytokines (IL- 6, LIF, G-CSF, GM-CSF, M-CSF, but not IL-1, IL-3, IL-7) were detected in HUVEC coculture supernatants. Neutralization of these cytokines pro foundly inhibited the ability of EC supernatants to support the differ entiation of hematopoietic progenitors and led to an accumulation of i mmature cells. Contact cocultures were significantly more efficient th an non-contact cocultures. The expanded cell population essentially be longed to the myeloid and monocytic lineages. Contact cocultures gener ated cells expressing the CD61 or CD41 antigens. Interleukin-1 alpha ( IL-1 alpha) augmented EC capacity to support hematopoiesis, this prope rty resulting from the upregulation of cytokine expression. Glucocorti coids (GC) reduced this capacity by downregulating the biosynthesis of cytokines by EC and not by a direct effect on the progenitor cells. E C from the bone marrow microvasculature (BMEC) support the proliferati on and the differentiation of hematopoietic progenitors. Synergistic i ncrease in progenitor cells expansion and generation of CFC occurred w hen EC cocultures were added with exogenous cytokines. Supernatants of IL-1 alpha-stimulated EC potentiated the effects of an association of IL-l, IL-3, IL-6, LIF, SCF, Flt3-ligand, TPD, G-CSF, GM-CSF, M-CSF an d IL-11 on the proliferation of hematopoietic progenitors suggesting t hat EC may produce other soluble growth factors potentiating the actio n of the above set of cytokines.