Absence of L-selectin results in increased survival following pulmonary irradiation

Full text: Irradiation results in increases of ICAM and VCAM expression in pulmonary endothelial cells preceding the development of irradiation-induced organizing alveolitis/fibrosis in C57BL/6J mice. There was no detectable increase in E-selectin or P-selectin in these studies (Epperly MW, et al. Pulmonary irradiation-induced expression of VCAM-1 and ICAM-1 is decreased by MnSOD-PL gene therapy. Biol. Blood Marrow Transplant., 8(4): 175-187, 2002). Following increases in ICAM and VCAM expression there was an infiltration of macrophages and fibroblasts into the area of organizing alveolitis/fibrosis. To determine whether adhesion molecules play a critical role in the development of irradiation-induced fibrosis, we irradiated ICAM, VCAM, E-selectin or L-selectin knockout mice to 20 Gy to the pulmonary cavity. The mice were followed for the development of organizing alveolitis/ fibrosis at which time the mice were sacrificed. There was no improved survival in irradiated ICAM, VCAM or E-selectin knockout mice. However, mice lacking L-selectin had an increased survival compared to littermate control, irradiated mice (p<0.001). To determine the degree to which mice developed organizing alveolitis/fibrosis, all mice were sacrificed when they became moribund. The lungs were expanded in OCT, removed, frozen in OCT, and sectioned. The lung sections were stained with hematoxylin and eosin (H and E) and examined for the development of organizing alveolitis/fibrosis using an optical imaging system. All mice developed detectable organizing alveolitis/fibrosis following irradiation. The results demonstrated that the absence of one adhesion molecule may not be sufficient to prevent organizing alveolitis/fibrosis. The results indicate the potential involvement of L-selectin in irradiation damage in the lung as demonstrated by increased survival of L-selectin knockout mice following irradiation. Further experiments will focus on the role of L-selectin in the development of organizing alveolitis/fibrosis