Inflammatory Reaction and Changes in Expression of Coagulation Proteins on Lung Endothelial Cells after Total-Body Irradiation in Mice
Résumé
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 γ 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. © 2003 by Radiation Research Society.
Mots clés
antibiotic agent
cell adhesion molecule
endothelial leukocyte adhesion molecule 1
enrofloxacin
fibrinogen
interleukin 6
messenger RNA
PADGEM protein
protein
thrombomodulin
thromboplastin
von Willebrand factor
animal model
animal tissue
article
bacterial infection
blood clotting
controlled study
down regulation
endothelium cell
enzyme linked immunosorbent assay
gamma radiation
gene expression
immunohistochemistry
inflammation
lung endothelium
male
mouse
nonhuman
pneumonia
priority journal
protein expression
radiation dose
radiation exposure
reverse transcription polymerase chain reaction
survival
whole body radiation
Animals
Anti-Bacterial Agents
Blood Coagulation
Chemokines
CXC
Endothelial Cells
Fibrinogen
Inflammation
Inflammation Mediators
Intercellular Signaling Peptides and Proteins
Interleukin-6
Lung
Male
Mice
Inbred C57BL
Whole-Body Irradiation
Bacteria (microorganisms)