Bone marrow stromal cells spontaneously produce Flt3-ligand: Influence of ionizing radiations and cytokine stimulation

Abstract

Purpose: To define the ability of human bone marrow (BM) stromal cells to produce fms-like tyrosine kinase 3 (Flt3)-ligand (FL), and the effect of irradiation, tumour necrosis factor-alpha (TNF) or tumour growth factor beta (TGF) on FL production.

Material and methods: Primary BM stromal cell cultures were irradiated at 2–10 Gy or were stimulated with TNFα or TGFβ1. The presence of FL was tested in culture supernatants and in cell lysate. The presence of a membrane-bound form of FL and the level of gene expression were also tested.

Results: Primary BM stromal cells spontaneously released FL. This production was increased by TNFα but not by TGFβ1 or by irradiation. Chemical induction of osteoblastic differentiation from BM stromal cells also induced an increase in FL release.

Conclusions: Our results suggest that the observed increase in FL concentration after in vivo irradiation is an indirect effect. The possible implication of BM stromal cells in these mechanisms is discussed.

Keywords:

• Ionizing radiations
• Flt3-ligand
• bone marrow
• stromal cells
• osteoblasts