title: Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis.
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.
authors: Division of Pneumoconiosis, School of Public Health, China Medical University, Heping District, Shenyang, China. sanqiaoyao@qq.com
authors: San-qiao
authors: SQ
authors: Yao
authors: Liying Wang
authors: LW
authors: Rojanasakul
authors: Zhi-yuan
authors: ZY
authors: Chen
authors: Ying-jun
authors: YJ
authors: Xu
authors: Yu-ping
authors: YP
authors: Bai
authors: Gang
authors: G
authors: Chen
authors: Xi-ying
authors: XY
authors: Zhang
authors: Chun-min
authors: CM
authors: Zhang
authors: Yan-qin
authors: YQ
authors: Yu
authors: Fu-hai
authors: FH
authors: Shen
authors: Ju-xiang
authors: JX
authors: Yuan
authors: Jie
authors: J
authors: Chen
authors: Qin-cheng
authors: QC
authors: He
mesh_terms: D000328:Adult; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor; D012822:Silicon Dioxide; D053148:Caspase 3; D053181:Caspase 8