In vivo
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Ionizing irradiation damage to the lung is associated with an acute inflammatory reaction, followed by a latent period and then late effects including predominantly pulmonary fibrosis. The cells mediating fibrosis have recently been shown to derive from the bone marrow hematopoietic microenvironment. Initiation of late pulmonary irradiation lung damage has been correlated with up-regulation of VCAM-1 and ICAM-1 in pulmonary endothelial cells, followed by infiltration of macrophages and bone marrow-derived fibroblasts forming the fibrotic lesions of organizing alveolitis/fibrosis. ⋯ As additional controls, transgenic Sod2 mouse long-term bone marrow cultures and those from HPV16, E6 and E7 cytokeratin 14 transgenic mice were also tested. No detectable difference in hematopoiesis was noted in these cultures compared to littermates. The results suggest a complex pattern of involvement of endothelial specific adhesion molecules and marrow fibroblasts in the cell biologic events associated with late irradiation pulmonary fibrosis.