Bone marrow stromal cells spontaneously produce Flt3-ligand: influence of ionizing radiations and cytokine stimulation.
OBJECTIVE
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 (TNFalpha) or tumour growth factor beta (TGFbeta) on FL production.


METHODS
Primary BM stromal cell cultures were irradiated at 2-10 Gy or were stimulated with TNFalpha or TGFbeta1. 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 TNFalpha but not by TGFbeta1 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.
Bertho
Jean Marc
JM
Laboratoire de radiotoxicologie experimentale, DRPH-SRBE, IRSN, Fontenay aux roses, France. jean-marc.bertho@irsn.fr
Demarquay
Christelle
C
Mouiseddine
Moubarak
M
Douenat
Noémie
N
Stefani
Johanna
J
Prat
Marie
M
Paquet
François
F
D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D010006:Osteoblasts / Q000166:cytology; D010641:Phenotype; D017154:Stromal Cells / Q000378:metabolism / Q000528:radiation effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008565:Membrane Proteins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein