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SULFUR MUSTARD VAPOR EFFECTS ON DIFFERENTIATED HUMAN LUNG CELLS.

Seagrave, JC., Weber, W.M. and Grotendorst, G.R. Lovelace Respiratory Research Institute, Albuquerque, NM, USA Inhalation Toxicology
Abstract

Context:  sulfur mustard (SM) causes skin blistering and long-term pulmonary dysfunction. Its adverse effects have been studied in battlefield-exposed humans, but lack of knowledge regarding confounding factors makes interpretation challenging. Animal studies are critical to understanding mechanisms, but differences between animals and humans must be addressed. Studies of cultured human cells can bridge animal studies and humans. Objective:  Evaluate effects of SM vapor on airway cells. Materials and methods:  We examined responses of differentiated human tracheal/bronchial epithelial cells, cultured at an air-liquid interface, to SM vapors. SM effects on metabolic activity (Water Soluble Tetrazolium (WST) assay), cytokine and metalloproteinase secretion, and cellular heme oxygenase 1 (HO-1), an oxidative stress indicator, were measured after 24 h. Results:  At noncytotoxic levels of exposure, interleukin 8 and matrix metalloproteinase-13 were significantly increased in these cultures, but HO-1 was not significantly affected. Discussion and conclusion:  Exposure of differentiated airway epithelial cells to sub-cytotoxic levels of SM vapor induced inflammatory and degradative responses that could contribute to the adverse health effects of inhaled SM.  

Keywords

EpiAirway (AIR-606), Cytokine production, Granulocyte colony-stimulating factor (G-CSF), Heme oxygenase 1 (HO-1), IL-6, IL-8, ,Interferon-inducible protein 10 (IP-10), Metalloproteinase secretion, MMP-1, MMP-13, MMP-3, MMP-7, MMP-9, Monocyte chemotactic protein 1 (MCP-1), Oxidative stress indicator, Sulfur mustard, Vascular endothelial growth factor (VEGF)

Materials Tested

Human parainfluenza viruses, Sialidase fusion protein

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