Background: Alveolar epithelial cells are known as progenitor cells for the restoration from the damage in the lung. Calcitonin gene-related peptide (CGRP) has been reported to play an important role in the proliferation of various types of epithelial and endothelial cells. We investigated the effects of CGRP on the proliferation of alveolar epithelial cells in vitro and in vivo.

We assessed the effects of long-term inhalation of toner on the pathological changes and formation of 8-hydroxydeoxyguanosine (8-OH-Gua) in DNA in a rat model. Female Wistar rats (10 wk old) were divided evenly into a high concentration exposure group (H: 15.2 mg/m(3)), a low concentration exposure group (L: 5.5 mg/m(3)), and a control group. The mass median aerodynamic diameter of the toner was 4.5 microm. The rats were sacrificed at the termination of a 1-yr or 2-yr inhalation period. Pathological examination was performed on the left lung, and the level of 8-OH-Gua in DNA from the right lung was measured using a high-performance liquid chromatography (HPLC) column. The pathological findings showed that lung cancer was not observed in any of the exposed or control groups, though pleural thickening and small foci of collagen were observed in toner-exposed rat lungs. Inhalation of the toner for 1 and even 2 yr did not induce the formation of 8-OH-Gua in DNA in rat lungs. These data suggest that long-term inhalation of toner may not induce lung tumors.

We assessed the effects of long-term inhalation of toner on the pathological changes and gene expression with the synthesis and degradation of collagenous extracellular matrix in a rat model. Female Wistar rats (10 wk old) were divided evenly into a high concentration exposure group (H: 15.2 mg/m3), a low concentration exposure group (L: 5.5 mg/m3), and a control group. The mass median aerodynamic diameter of toner was 4.5 microm. The rats were sacrificed at the termination of a 1-yr or 2-yr inhalation period. Pathological examination was performed from the left lung, and transcriptional levels of mRNA extracted from the right lung were assessed by semiquantitative reverse-transcription polymerase chain polymerase (RT-PCR). The pathological findings showed mild pulmonary fibrosis in 20% (L, 1 yr), 40% (H, 1 yr), 56% (L, 2 yr) and 62% (H, 2 yr), while lung cancer was not observed in any of the exposed groups. In the 1-yr high-concentration group, gene expression of matrix metalloproteinase-2 (MMP-2) and type I collagen mRNA in the rat lungs increased, while tissue inhibitors of metalloproteinase-2 (TIMP-2) decreased. The 2-yr high-concentration group increased in message level of type I collagen and TIMP-2 but not that of MMP-2. These data suggested that results of gene expression of MMP, TIMP, and collagen in the 2-yr exposure may lead to accumulation of collagen compared to the 1-yr exposure, and that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix might be associated with pulmonary fibrosis induced by toner.

Gene Expression of Clara Cell Secretory Protein, Surfactant Protein-A and Thyroid Transcription Factor-1 in the Lungs of Rats Exposed to Potassium Octatitanate Whiskers in vivo: Li DING, et al. Institute of Industrial and Ecological Sciences, University of Occupational and Environmental Health, Japan-Inhalation studies have shown that exposure to potassium octatitanate whiskers (PT1), an asbestos substitute, produces pulmonary fibrotic changes, suggesting that PT1 might have fibrogenic potential. It has been theorized that Clara cell secretion protein (CCSP) and surfactant protein-A (SP-A) play a critical role in regulating the acute inflammatory response in the lung. The present study was conducted to investigate the time course (3 days, 1 wk, 1 month, 3 months, and 6 months) of the expression of mRNA of CCSP, SP-A and thyroid transcription factor 1 (TTF-1), a common transcription factor of CCSP and SP-A, in lungs exposed to PT1 in vivo. PT1 suspended in saline was administered to male Wistar rats at a dose of 2 mg or 10 mg by single intratracheal instillation, and RNA was then extracted from the lungs. Expression of CCSP, SP-A and TTF-1 mRNA from the lungs was examined by reverse transcription-polymerase chain reaction. Exposure to 2 mg of PT1 did not increase levels of CCSP, SP-A or TTF-1 mRNA. The level of SP A mRNA in PT1 -exposed rats was decreased at 1, 3 and 6 months after a single instillation of 10 mg. Levels of CCSP and TTF-1 mRNA were also decreased at 3 days, 3 and 6 months after a single instillation. These findings suggest that CCSP and SP-A are involved not only in the acute inflammatory response but also in the chronic response of the lung exposed to PT1.

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