Expression of Flt3-ligand by the endothelial cell

Flt3-ligand (FL) is a cytokine that is of paramount importance in the proli feration of primitive hematopoietic progenitors. In this study, we show tha t endothelial cells (EC) produce large amounts of soluble FL and express a membrane-bound form of the molecule. Bone marrow microvascular EC also prod uce FL, suggesting that EC are an important source of FL in the bone marrow . High concentrations of FL in EC supernatants contrast with its undetectab le levels in long-term bone marrow cultures. A single mRNA for FL is detect ed, suggesting that soluble FL derives from the membrane-bound species by p roteolytic release. FL mRNA is stable with a half-life of about 3 h. II-1 a lpha increases FL mRNA levels and membrane and soluble FL expression. Gluco corticoids, known inhibitors for many hematopoietic growth factors do not d own-regulate the expression of FL. On the contrary, GC increase the express ion of both species of FL. The neutralization of FL in cocultures EC/hemato poietic progenitors results in an acceleration of the maturation of the pro genitors. IFN-alpha, MIP-1 alpha and TGF-beta stimulate production of membr ane-bound and soluble FL. This stimulation is essential to explain their mo dulatory effect on the generation of clonogenic cells in cocultures EC/hema topoietic progenitors.