Abstract

Keywords

Expression of Flt3-ligand by the endothelial cell

A Solanilla¹, C Grosset¹, C Lemercier¹, M Dupouy¹, FX Mahon¹, K Schweitzer², J Reiffers¹, B Weksler³ & J Ripoche¹

Correspondence to: A Solanilla, Laboratoire de Greffe de Moelle, Université Victor Ségalen, Bordeaux II, 146, rue Léo Saignat, 33076, Bordeaux, France; Fax: (33) 05 56 93 88 83

Flt3-ligand (FL) is a cytokine that is of paramount importance in the proliferation of primitive hematopoietic progenitors. In this study, we show that endothelial cells (EC) produce large amounts of soluble FL and express a membrane-bound form of the molecule. Bone marrow microvascular EC also produce FL, suggesting that EC are an important source of FL in the bone marrow. High concentrations of FL in EC supernatants contrast with its undetectable levels in long-term bone marrow cultures. A single mRNA for FL is detected, suggesting that soluble FL derives from the membrane-bound species by proteolytic release. FL mRNA is stable with a half-life of about 3 h. II-1 increases FL mRNA levels and membrane and soluble FL expression. Glucocorticoids, known inhibitors for many hematopoietic growth factors do not down-regulate the expression of FL. On the contrary, GC increase the expression of both species of FL. The neutralization of FL in cocultures EC/ hematopoietic progenitors results in an acceleration of the maturation of the progenitors. IFN-, MIP-1  and TGF- stimulate production of membrane-bound and soluble FL. This stimulation is essential to explain their modulatory effect on the generation of clonogenic cells in cocultures EC/hematopoietic progenitors. Leukemia (2000) 14, 153–162.

^© Macmillan Publishers Ltd 2000