Endothelial injury and repair in radiation-induced pulmonary fibrosis

Abstract

Cytokinetic relationships between endothelial cells and fibroblasts during lung injury and repair in mice have been studied in a morphologic, autoradiographic, and biochemical study following whole body irradiation. After 650 rads, endothelial injury accompanied by interstitial edema was seen between weeks 1 and 2. The cell labeling curve had two components: predominant endothelial labeling to 3 weeks, then a smaller rise in DNA synthesis in interstitial cells. There was focal fibrosis but little change in total hydroxyproline to 20 weeks. After 1000 rads, cell injury, still confined to the endothelium, was more severe and lasted up to 6 weeks. Increased DNA synthesis occurred in the endothelium between Weeks 2 and 8 and in interstitial cells from Week 3 to 16, when total hydroxyproline was significantly elevated and many fibrotic areas were seen in the lung. The results indicate that acute endothelial injury may be rapidly repaired with little fibroblastic stimulation, whereas severe or prolonged injury with delayed regeneration disturbs endothelial-mesenchymal relationships. This may be a key factor in promoting fibroblast proliferation and the deposition of collagen.