Changes in Autacoid and Neuropeptide Contents of Lung Cells in Asbestos-induced Pulmonary Fibrosis

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Abstract
The purpose of this study was to determine if asbestos-induced pulmonary fibrosis in the rat can affect the levels of autacoids and peptides in freshly isolated lung cells. Lung fibrosis was experimentally induced in rats by a single intratracheal instillation of 5 mg UICC Canadian chrysotile B fibers. Isolated lung cells were prepared from normal and from asbestos-exposed rats. These cells were also fractionated on bovine serum albumin (BSA) gradients. The contents of serotonin (5-HT), histamine (HIST), vasoactive intestinal peptide (VIP), and bombesin (BN) were measured in isolated total cell preparations as well as in density-fractionated cell populations from normal and from asbestos-exposed rats. Analysis of total lung cell preparation showed the presence of heterogeneous populations in normal rat lung. After asbestos exposure, there were significant changes in these cell populations as evidenced by significant increases in lymphocyte and mast cell numbers. In addition, increased levels of 5-HT, HIST, and VIP were observed in isolated lung cells obtained from rats exposed to asbestos 1, 3, and 6 months after instillation. BN content was unchanged 3 months after treatmeant, but was significantly increased at the 6 month-interval, suggesting a different pattern of responses for this neuropeptide. Density fractionation of various cell populations further showed selective changes in specific cell fractions of lung after asbestos exposure. At 6 months, increased levels of 5-HT, HIST, and VIP were associated with cell fraction 7% whereas changes in BN content were found in cell fractions 2 and 3. Similarly, there was a significant increase of mast cells in fraction 7 at the 6-month interval. The parallel pattern of changes obtained for HIST, VIP, and 5-HT with mast cell number supports the assumption that higher levels of these mediators is due to increased mast cells. On the other hand, changes in BN content appeared to involve other cell populations and may reflect changes in neuroendocrine cells (NEC) or a subset of these. Moreover, while mast cell numbers increased at an earlier interval, BN-containing neuroendocrine cells were affected at a later time after asbestos exposure.