Inflammatory reaction and changes in expression of coagulation proteins on lung endothelial cells after total-body irradiation in mice.
Inflammatory reaction is a classical feature of radiation exposure, and pneumonitis is a dose-limiting complication in the handling of hematological disorders treated with total-body irradiation. In the present study, we first evaluated the inflammatory response in C57BL6/J mice exposed to lethal doses of gamma rays treated with antibiotics or not. Both interleukin 6 and KC (also known as Gro1) were increased in the plasma 10 to 18 days after radiation exposure, independent of bacterial infection, whereas fibrinogen release was linked to a bacterial infection. Furthermore, both Il6 and KC were increased in the lungs of irradiated mice. Our second objective was to characterize the endothelial cell changes in the lungs of total-body-irradiated mice. For this purpose, a quantitative RT-PCR was used to determine the expression of genes involved in inflammatory and coagulation processes. We found that the adhesion molecules P-selectin and platelet endothelial cell adhesion molecule 1 were up-regulated, whereas E-selectin remained unchanged. Tissue factor expression was up-regulated as well, and thrombomodulin gene expression was down-regulated. The investigation by immunohistochemistry of adhesion molecules confirmed the increase in the basal expression of both P-selectin and platelet endothelial cell adhesion molecule 1 on pulmonary endothelial cells. All together, our results suggest the involvement of endothelial cells in the development of radiation-induced inflammatory and thrombotic processes.
Van der Meeren
Anne
A
Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection de la santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, Fontenay-aux-Roses cedex, France. anne.vandermeeren@irsn.fr
Vandamme
Marie
M
Squiban
Claire
C
Gaugler
Marie-Hélène
MH
Mouthon
Marc-André
MA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001777:Blood Coagulation / Q000528:radiation effects*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000097:blood; D042783:Endothelial Cells / Q000502:physiology / Q000528:radiation effects*; D005340:Fibrinogen / Q000032:analysis; D007249:Inflammation / Q000209:etiology*; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014916:Whole-Body Irradiation
D000900:Anti-Bacterial Agents; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D005340:Fibrinogen