203 Heightened levels of microvesicle particles resulting from combination of ethanol and thermal burn injury

Abstract

Ethanol, in combination with thermal burn injury, is a clinically significant problem resulting in an increase in morbidity and mortality due to acute multi-organ toxicity from excess systemic cytokine release. Moreover, murine models of intoxicated burn injury replicate the acute toxic effects as well as a delayed systemic immunosuppression. Almost half of the admitted hospital patients with burn injuries were alcohol intoxicated at the time of admission. Our group has demonstrated that the lipid mediator Platelet-activating factor (PAF) plays an important role in the delayed immunosuppressive effects of intoxicated thermal burn injury. As PAF receptor signaling causes generation of subcellular microvesicle particles (MVP), the objective of the present studies is to define the role of MVP in the toxicity associated with EtOH + burn injury. Using HaCaT keratinocyte-derived cell line, we demonstrate that both thermal burn injury and EtOH alone generate increased release of MVP into the supernatant. Combining the two agents results in an increased generation of MVP in at least an additive fashion. These studies suggest that MVP might play a role in the augmented toxicity of intoxicated thermal burn injury.