Mast Cells are Key Mediators to the Pulmonary Inflammatory Response to Chloropicrin Exposure 4838

Abstract Description Mast cells (MCs) are located throughout the lung and are readily capable of rapid activation, degranulation, and cytokine release after exposure to xenobiotics, leading to allergic inflammation and disease. Little is known about the contribution of mast cells on cell recruitment, inflammation, and lung pathology from acute exposure to chloropicrin, a known fumigant and anti-riot agent. To further understand the role MCs play in inflammation pathology, we exposed wild type (WT, C57BL/6) mice and mice lacking functionally mature MC (mast cell deficient mice, cKitW-sh) to chloropicrin ranging from 0.1 to 20mg/kg via oropharyngeal instillation. Results show that WT mice had increased inflammatory indicators including cell influx into the airspace, dominated by neutrophils. Severe pathologic damage to the alveoli was seen in WT only. Cytokine profiles revealed increases in IL-6, IL-8, IL-13, IL-17, and IL-33 in WT mice but largely absent in cKitW-sh mice. Flow cytometry revealed significant increases in neutrophils, both alveolar and interstitial macrophage populations, and differences in dendritic cell (both cDC1 and cDC2) populations in WT mice. In contrast, increases in neutrophils, interstitial macrophages and dendritic cells were less pronounced in cKitW-sh mice.The data suggest that MC play a significant role in lung inflammation and pathology following chloropicrin exposure which could inform future medical interventions and treatments related to exposure events. Funding Sources Funding was provided by NIH, NIEHS grant R56ES034386 and T32ES029074 and the University of Colorado Cancer Center Support Grant (P30CA046934). Topic Categories Mucosal and Regional Immunology (MUC)