Document Type

Poster

Publication Date

5-3-2021

Identifier/URL

39890890 (Pure)

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 acEthanol, in combination with thermal burn injury, is a clinically significant problem resultingin an increase in morbidity and mortality due to acute multi-organ toxicity from excesssystemic cytokine release. Moreover, murine models of intoxicated burn injury replicate theacute toxic effects as well as a delayed systemic immunosuppression. Almost half of theadmitted hospital patients with burn injuries were alcohol intoxicated at the time of admis-sion. Our group has demonstrated that the lipid mediator Platelet-activating factor (PAF) playsan important role in the delayed immunosuppressive effects of intoxicated thermal burninjury. 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 asso-ciated with EtOH + burn injury. Using HaCaT keratinocyte-derived cell line, we demonstratethat both thermal burn injury and EtOH alone generate increased release of MVP into thesupernatant. Combining the two agents results in an increased generation of MVP in at leastan additive fashion. These studies suggest that MVP might play a role in the augmentedtoxicity of intoxicated thermal burn injury.ute 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 an additive fashion. In addition, the effect a prominent CPLA2 inhibitor to block PAF synthesis was investigated on the stimulation of MVP release due to thermal burn injury. We looked at the inhibition in the CPAF and TPA pathways to demonstrate that thermal burn injury uses CPLA2 in its mechanism to release MVPs while TPA does not. These studies suggest that MVP might play a role in the augmented toxicity of intoxicated thermal burn injury.

Comments

Presented at the 2021 Society for Investigative Dermatology Virtual Meeting, May 3-8, 2021.

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