Sulfur mustard vapor effects on differentiated human lung cells

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::

• Sulfur mustard
• in vitro
• cytokines
• matrix metalloproteinases
• heme oxygenase-1

Acknowledgements

The authors gratefully acknowledge the technical contributions of Guy Herbert, Lois Herrera, Mericka Lehman, and David Palucki.

Declaration of interest

This work supported by a Cooperative Agreement from the National Institute of Neurological Diseases and Stroke, National Institutes of Health (grant number 5U54NS058185-03). The authors alone are responsible for the content and writing of this paper.