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Abstract ID 97752 Poster Board 013 1. Department of Pharmacology and Toxicology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI. 2. Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 3. Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO. Sulfur Mustard (SM) has been a widely used chemical warfare weapon since World War 1 with the potential to be weaponized for terrorism. Despite international efforts to curb the use of chemical weapons, the risk of the use of SM remains a great concern due to its recent employment in countries like Syria and existing stockpiles. SM exposure mainly causes debilitating injuries to the lung, eye, and skin tissues. Injuries of this toxicant to the skin include blistering, secondary infections, and systemic effects. Lung injury is the most common cause of mortality from SM exposure and leads to long-term toxic effects. In our previous studies in mice, we have observed mortality with skin morbidity following acute cutaneous exposure to SM analog nitrogen mustard (NM). Vesicant skin exposure can lead to absorption causing systemic injury to organs, including the lungs; however, there is limited research available. Hence, we examined lung injury from a single acute cutaneous NM exposure in mice in this study. Understanding the toxic effects and mechanisms of acute vesicant skin exposure, especially to the lung tissue, can allow for a better understanding of systemic toxic effects and aid the development of therapies against this exposure. Based on our studies in the skin tissue following NM cutaneous exposure in mice which indicated a role of mast cells in NM-induced skin injury, we will investigate if mast cells are activated in the lung following cutaneous NM exposure. The dorsal skin of C57BL/6 mice was exposed to 1 mg of NM dissolved in 100 μL of acetone or 100 μL of acetone alone as vehicle control. Following clinical observations and assessments, mice were sacrificed, and tissues were collected for analysis on day 1, day 3, and day 8 post-NM exposure. Hematoxylin and Eosin (H&E) staining was performed to allow for analysis of lung morphology and lesions. PCR analysis was performed to measure the expression of inflammatory markers in lung tissue samples. Intact and degranulated mast cells were counted after toluidine blue staining of the lung tissue samples. H&E staining showed necrotizing bronchiolitis, alveolitis, and intestinal edema post-day 1 of NM exposure in mice. NM caused widespread accumulation of extravascular erythrocytes in both parenchymal tissue and alveolar airspaces. Areas of marked to moderate edema of proteinaceous exudate were evident in NM-exposed mice lungs, probably consisting of fibrin, which spread to small airways and alveoli. PCR results further confirmed the inflammatory effects of NM in the lung tissue with significant time-dependent increases in the expression of inflammatory cytokines, IL-1β and TNF- α, which were elevated at days 1-8 post-exposure compared to the control group. In addition, mast cell degranulation increased in the mouse lung tissue at days 1 and 8 post-NM exposure when compared to the control lung samples. These novel findings show lung injury and inflammatory effects in mice from NM cutaneous exposure. We are further analyzing the lung tissue samples to better characterize the progression of lung injury from NM cutaneous exposure and the role of mast cells in the mechanism of vesicant lung injury.
Veluru et al. (Mon,) studied this question.