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Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis

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Abstract

In vitro and in vivo studies have demonstrated that lung cell apoptosis is associated with lung fibrosis; however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers, and 13 male healthy volunteers. The relationships between apoptosis index (AI) and silica exposure history, soluble Fas (sFas)/membrane-bound Fas (mFas), and caspase-3/caspase-8 were analyzed. AI, mFas, and caspase-3 were significantly higher in lung lavage fluids from silicosis patients than those of observers or healthy volunteers, but the level of sFas demonstrated a decreasing trend. AI was related to silica exposure, upregulation of mFas, and activation of caspase-3 and -8, as well as influenced by smoking status after adjusting for confounding factors. These results indicate that AM apoptosis could be used as a potential biomarker for human silicosis, and the Fas/FasL pathway may regulate this process. The present data from human lung lavage samples may help to understand the mechanism of silicosis and in turn lead to strategies for preventing or treating this disease.

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Acknowledgment

We would like to acknowledge the other staff from the Department of Pneumoconiosis of “Beidaihe Sanatorium for China Coal Miners” for whole-lung lavage, and also appreciate those who assisted us at Hebei United University and China Medical University. We also would like to give thanks to BioMed Proofreading, LLC for their careful copy editing. The programs were supported by the Natural Science Foundation of China (30671741), Pneumoconiosis Treatment Foundation for China Coal Miners (2005-03), and Science and Technology Support Program of Hebei Province (09276196D).

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The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

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Correspondence to Qin-cheng He.

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Yao, Sq., Rojanasakul, L.W., Chen, Zy. et al. Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis. Apoptosis 16, 1195–1204 (2011). https://doi.org/10.1007/s10495-011-0647-4

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