Mast cells and biogenic amines in radiation-induced pulmonary fibrosis

Sprague-Dawley rats were exposed to a single X-ray dose of 30 Gy over the lungs and examined at 1-wk intervals during the following 3 to 8 wk. Mast cells were counted after specific staining with toluidine blue at a low pH and the mast-cell amines, histamine (Hi) and serotonin (5-HT), were measured using high-performance liquid chromatography. Irradiation induced pneumonitis followed by pulmonary mast-cell hyperplasia and progressive fibrosis 4 to 8 wk after irradiation. By week 4, immature-looking mast cells with a few granules started to appear, followed by a gradual increase in mast cells that reached very high levels after 8 wk, up to 40 to 200 times the normal. The pulmonary Hi and 5-HT content increased concomitantly from 6 and 1 micrograms/g to a maximum of 200 and 18 micrograms/g, respectively. These high levels of amine content and mast-cell densities greatly exceed those of any normal tissue. There was a strong correlation between the Hi and 5-HT content in both normal (r = 0.87) and irradiated (r = 0.93) lung tissue, as well as between the mast-cell density and amine content after irradiation (r = 0.86), thereby indicating that both amines derived from mast cells. The Hi/5-HT quotients were much lower in both normal and irradiated lung tissue (5 and 9, respectively) than in other tissues where these amines are stored in mast cells, or in isolated peritoneal mast cells (43). This relatively higher 5-HT content in pulmonary mast cells suggests that this amine performs a specific function in the lung.