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Lovelace CRCE Research Project 2: Mechanism of Sulfur Mustard Induced Lung Injury

Exposure to Sulfur Mustard (SM) aerosols causes serious acute and chronic injuries, primarily to the lung, skin, and eyes. Presently, there are no effective treatments for SM injury. A major hurdle in the development of rational therapeutic interventions for SM injury is a lack of understanding of the mechanism of SM-induced lung injury.

Based on published data, we propose that SM injury to the lung is caused by two events:
  • Alkylating activity of SM rapidly modifies cellular proteins, and initiates both an acute (inflammation) and chronic (adaptive) immunological response, leading to a chronic autoimmune status
  • SM inhibition of acetylcholinesterase, which causes acute bronchoconstriction, bronchospasms, and exacerbated asthma
Accordingly, we propose to:
  • Evaluate the role of inflammation in SM-induced lung injury
  • Examine the effects of acute SM inhalation on airway resistance
  • Ascertain the effects of SM exposure on the development of adaptive immunity
  • Examine the effects of potential therapeutic agents (particularly combination therapies) on the acute and chronic toxicities of SM exposure
We believe these studies will provide a rational approach for the identification of Top Countermeasure Therapeutics (TCTs).


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