Microvesicles in thermal burn injury Evidence for Microvesicle Particles and Platelet-activating Factor as Effectors for Systemic Effects of Thermal Burn Injury

Akhil V Parackal¹Richard C Fox¹Aadil Umerani¹Youngjun Park¹R Michael Johnson¹Wenfeng Zhang¹Zheng Xu²Alison Smith³Craig A Rohan¹Jeffrey B Travers^1*

• ¹Boonshoft School of Medicine, Wright State University, Dayton, United States
• ²Wright State University, Dayton, United States
• ³LSU Health New Orleans School of Medicine, New Orleans, United States

ABSTRACT Thermal burn injury (TBI) is an important source of morbidity and mortality. The exact mechanisms for the systemic effects including multiple organ dysfunction (MOD) and immune deficits associated with extensive skin burn injuries are unclear and this knowledge gap has negatively impacted therapy. The goal of this review is to present evidence for a model of TBI-induced systemic effects that involves skin keratinocyte release of subcellular microvesicle particles (MVP) carrying the potent lipid mediator Platelet-activating Factor (PAF) as effectors. As TBI has been shown to generate high levels of potent 1-alkyl PAF versus lesser amounts of inhibitory 1-acyl PAF species, it would be expected that MVP produced by burn would be highly powerful PAF receptor agonists. In addition, we present results of a pilot study with 12 human subjects suggesting that MVP can be measured systemically within hours following a TBI. This model involving MVP provides an explanation for why advanced age and ethanol intoxication result in worsening systemic effects including MOD following a TBI. The need for more clinical studies in this critical area of TBI pathogenesis is also discussed. Potential therapeutic implications of this model will also be addressed. An improved understanding of how a significant skin burn injury results in systemic manifestations will result in improved TBI patient outcomes and could be applicable to other environmental stressors.