Sequential implication of lymphoid and stromal cells in FL variation after irradiation in mice.
Marie PRAT, Christelle DEMARQUAY, Johanna FRICK, Dominique THIERRY,Norbert-Claude GORIN, and Jean-Marc BERTHO, European Radiation Research, 25-28/08/2004, Budapest, Hongrie.
Objective: We previously showed that plasma FL concentration was increased after irradiation and that this increase was correlated to the numbers of bone marrow surviving progenitor, reflecting bone marrow function during radio-induced aplasia. We thus investigate which organ or cells are implicated in FL concentration increase post irradiation. Methods: Balb/C mice and NOD/SCID mice were irradiated at doses of 6 Gy and 4 Gy respectively. At various time after irradiation, bone marrow, spleen, liver, brain, thymus and blood cells were analysed for FL mRNA expression by RT-PCR. We also quantified the FL protein in each tissue. Results: We showed that in bone marrow, spleen, liver and brain of Balb/C mice, only weak variations in FL mRNA expression were observed. Major changes were observed in WBC with a 6,33 ± 0,68 fold increase on day 3 after irradiation, and in thymus with a first 3,68 ± 0,88 fold increase on day 3 followed by a second 10,8 ± 4,3 increase on day 21. In order to confirm the implication of these tissues in FL regulation after irradiation, we performed FL quantification at day 3 in these organs. After irradiation, no significant variation were observed in brain and liver, while a significant decrease in FL quantity was observed in the bone marrow. By contrast, an increase in FL quantity was observed in spleen, thymus and WBC. These results suggest that T lymphocytes are strongly implicated in radio-induced plasma FL increase. We thus investigate variation in FL concentration in irradiated NOD/SCID mice, which are devoided of T lymphocytes. FL mRNA expression was different as compared to Balb/C mice with a 4-fold increase in FL mRNA expression at day 28, and a higher FL mRNA expression in WBC. A weak expression was observed in the thymus. Despite these major changes of FL mRNA expression as compared to Balb/C mice, the quantity of FL detected on day 3 in these organs was similar in the 2 strains of mice. Thus, the lack in T lymphocytes modified the pattern of FL mRNA expression in the organs without affecting the FL production. Conclusions: Our results suggest that T lymphocytes are not solely implicated in radiation induced increase in FL concentration, and that other cell types, such as endothelial cells or stromal cells might be strongly implicated.