The overall objectives of this project are to explore how nucleic acids released from dead and dying cells following irradiation induce inflammation and coagulation factor consumption and to determine if nucleic acid scavengers can mitigate such effects and prolong survival.
The specific aims are: 1) To explore how extracellular DNA/RNA and nucleic acid-containing complexes released from dead and dying cells following irradiation activate innate immune responses and induce inflammation and/or activate the contact pathway of coagulation and result in coagulation factor consumption. 2) To determine if nucleic acid scavengers can bind and counteract proinflammatory and procoagulant effects of irradiation associated nucleic acids and nucleic acid-containing complexes in cell culture and coagulation assays. 3) To determine if nucleic acid scavengers can improve survival of animals following lethal irradiation and reduce inflammatory shock and coagulation factor consumption and associated bleeding following irradiation without compromising the ability of the animals to respond to infection.
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