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Saturday 20, November, 2004 09:30 - 12:30, 3 hours, International Conference Hall Plenary Session 4 Medical Aspects: Surveillance and Treatment of Asbestos-related Diseases 4-A: Asbestos and Non-asbestos Agents in Mesothelioma Pathogenesis and Immunology Chairs: Yasunosuke Suzuki and Iguchi Hiroshi Yasumitsu Nishimura, Tamako Nishiike, Yasuhiko Wada, Hiroshi Iguchi Department of Hygiene, Hyogo College of Medicine, Japan ABSTRACT: Alveolar macrophages (AMs), which can produce TGF- as well as induce inflammation, has been thought to play a critical role to evoke the lung fibrogenesis in asbestosis. In the present study, we performed the experiments of intratracheal instillation with chrysotile B (CH) to Wistar male rats and in vitro exposure with CH to AMs to examine the production of TGF- 1, apoptosis and the generation of multinucleated giant cells (MGCs) by the AMs. After 5 days of the instillation with 4 mg of CH, BALF recovered from the rats showed the increases in TGF- 1 production, annexin (Anx)+PI- early apoptotic cells, Anx+PI+ late apoptotic cells and DNA-degradated cells, and showed additionally the generation of MGC. The AMs in this BALF produced a significantly higher amount of TGF- 1 in the culture for 5 days than those from the control group of rats. In accordance with this result, the AMs from the control group produced a high amount of TGF- 1 in the culture with 10 g/ml CH, which were comparable to the AMs from the rats instilled with CH. However, the apoptosis of AMs were not induced at this condition of the culture, while 50 g/ml CH markedly induced the apoptosis and increased Anx+PI-, Anx+PI+ and DNA-degradated cells sequentially. CH and the induced apoptotic cells did not directly induce the generation of MGC by AMs in vitro, in contrast to the results of the intratracheal instillation with CH. These results indicate that AMs can augment autonomously the production of TGF 1 regardless of the interaction with lung epithelial cells or fibroblasts, and that the apoptosis and the augmented production of TGF- 1 by AM exposed to CH are independent each other and which response to induce depends only on the dose of CH. Suppression of the AM with such fibrogenic ability may be crucial to prevent from the progress of lung fibrogenesis. |