Asbestos-induced fibrosis in rats: increase in lung mast cells and autacoid contents.

Adult male Wistar rats were treated with one tracheal instillation of 5 or 10 mg chrysotile B asbestos fibers in 0.5 ml saline, or 0.5 ml saline only (controls). Rats were killed at 1, 3, and 6 months postinstillation. Serotonin and histamine were quantitated in lung tissue homogenate using high-performance liquid chromatography with electrochemical and fluorometric detection, respectively. Serotonin was also quantitated in the cytoplasm of grouped (NEB) and individual (NEC) neuroendocrine cells and in mast cells using formaldehyde vapor-induced fluorescence and microspectrofluorometry, and density indices of NEBs, NECs, and mast cells were determined. Tissue edema, fibrotic lesions, and medial hypertrophy of pulmonary arterioles were assessed morphometrically. Test rats had higher pulmonary serotonin and histamine levels than controls at 1, 3, and 6 months. They also had higher cellular serotonin in NEBs at 1 month, but not in NECs, and tended to have higher serotonin levels in mast cells at 6 months. Mast cell numbers were higher among tests at 1 and 3 months, whereas NEBs and NECs were unchanged by asbestos. There was no difference between tests and controls in the amount of tissue edema at any time. However, all test rats had distinct lung lesions characterized by peribronchiolar fibrosis and bronchiolitis obliterans. No such lesions were present among control rats. Typically, mast cells were located immediately beneath the epithelial basal lamina of the bronchiolar fibrotic projections and at their stalks, whereas no mast cells were noted beneath normal epithelium, indicating a role of mast cells in asbestos-induced peribronchiolar fibrosis. Moreover, arteriolar medial hypertrophy at all three ages in conjunction with the increased levels of serotonin was an index of putative chronic pulmonary hypertension. Our results suggest that asbestos-induced rises in serotonin and histamine are due primarily to increased numbers of mast cells.