Lung inflammatory models for the development of countermeasures against vesicants

我们研究的总体目标是阐明巨噬细胞和炎症介质在泡泡剂引起的急慢性肺损伤中的作用，并确定治疗干预的长期目标。我们假设巨噬细胞在发泡剂的肺毒性中起双重作用。而最初经典活化的M1巨噬细胞通过释放过量的促炎/细胞毒性介质导致急性组织损伤，随后释放

The overall goal of our research is to elucidate the role of macrophages and inflammatory mediators in acute and chronic pulmonary injury induced by vesicants with the long-term objective of identifying targets for therapeutic intervention. We hypothesize that macrophages play a dual role in the pulmonary toxicity of vesicants. Whereas initially classically activated M1 macrophages contribute to acute tissue injury by releasing excessive quantities of proinflammatory/cytotoxic mediators, subsequent release of mitogenic and fibrogenic mediators by overactive M2 macrophages leads to chronic injury including pulmonary fibrosis. Using sulfur mustard and nitrogen mustard as model vesicants, plans are to determine if M1 and M2 macrophage subpopulations differentially contribute to the acute and long-term consequences of vesicant intoxication, and if pharmacologically modifying their activity or mediators they release mitigates toxicity. Working with the Medicinal Chemistry and Pharmaceutics Core, we also plan to engineer and evaluate an injectable lung delivery system consisting of poly(ethylene glycol) hydrogel particles (