Grant: Operating Grant

Inhalation of chlorine from acccidental spills or from acts of terrorism causes severe airway damage that is caused by the reactive nature of chlorine. Oxidation of many cellular proteins occurs and inflammation is triggered. The damage is almost certainly largely attributable to hypochlorous acid which is also a major product of neutrophils, a common cell involved in acute inflammation. We have demonstrated that cysteinyl-leukotrienes, compounds usually associated with allergic reactions, are released following chlorine. Although usually associated with pathology it appears that leukotrienes exert protective effects through actions on the principal receptor for their actions in the airways CysLTr1. We propose to elucidate the novel protective role of leukotrienes against the oxidative injury caused by chlorine and to explore the possibility that defective anti-oxidant mechanisms underly the susceptibility related to CysLTr1 deficiency.