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SM activated all four caspases in cells obtained from bronchoalveolar lavage fluid (BALF) as early as 6 h after exposure. Caspase-8, which is known to initiate the extrinsic Fas-mediated pathway of apoptosis, was increased fivefold between 6 and 24 h, decreasing to the unexposed-control level at 48 h. The initiator, caspase-9, in the intrinsic mitochondrial pathway of apoptosis as well as the executioner caspases, caspase-3 and -6, all peaked ( P &lt; 0.01) at 24 h; caspase-3 and -6 remained elevated, but caspase-9 decreased to unexposed-control level at 48 h. To study further the Fas pathway, we examined soluble as well as membrane-bound Fas ligand (sFas-L and mFas-L, respectively) and Fas receptor (Fas-R) in both BALF cells and BALF. At 24 h after SM exposure, sFas-L increased significantly in both BALF cells ( P &lt; 0.01) and BALF ( P &lt; 0.05). However, mFas-L increased only in BALF cells between 24 and 48 h ( P &lt; 0.1 and P &lt; 0.001, respectively). Fas-R increased only in BALF cells by 6 h ( P &lt; 0.01) after SM exposure. Apoptosis in SM-inhaled rat lung specimens was also confirmed by both immunohistochemical staining using cleaved caspase-3 and -9 antibodies and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining as early as 6 h in the proximal trachea and bronchi, but not before 48 h in distal airways. These findings suggest pathogenic mechanisms at the cellular and molecular levels and logical therapeutic target(s) for SM inhalation injury in animals.<\/jats:p>","DOI":"10.1152\/ajplung.00281.2015","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:20:32Z","timestamp":1490919632000},"page":"L959-L968","source":"Crossref","is-referenced-by-count":9,"title":["Apoptotic cell death in rat lung following mustard gas inhalation"],"prefix":"10.1152","volume":"312","author":[{"given":"Devon K.","family":"Andres","sequence":"first","affiliation":[{"name":"Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Aberdeen, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Keyser","sequence":"additional","affiliation":[{"name":"Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Aberdeen, 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