Extracellular Mitochondria in Sepsis-Induced Acute Respiratory Distress Syndrome

Abstract

Sepsis-induced acute respiratory distress syndrome (ARDS) is a life threatening disease that is associated with high mortality rates, and high hospital costs. The body’s widespread and aggressive inflammatory response to infection plays a central role in this condition, as it results from a rampant generation of inflammatory cytokines and reactive oxygen species in response to pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). Despite the seriousness of this condition, successful treatment strategies and effective biomarkers remain elusive. Here we aim to mimic a state of sepsis-induced ARDS in vitro and examine the response of extracellular mitochondria under these conditions. Additionally we aim to examine the proteomic profile of the extracellular mitochondrial pellet in a state of oxidative stress compared to control. Finally we aim to demonstrate that extracellular mitochondria are present in an in vivo model of sepsis-induced ARDS using a porcine model. From this work we are able to conclude that cells release mitochondrial DNA in response to both lipopolysaccharide and hydrogen peroxide treatments, however the mechanism by which this occurs remains unclear. Extracellular mitochondrial DNA is also present in an in vivo porcine sepsis-induced ARDS model. From proteomic analysis of the extracellular mitochondrial pellet by liquid chromatography - mass spectrometry, we found 16 proteins to be significantly (P<0.10) up-regulated and 2 proteins to be significantly down-regulated. We hope to apply the profile of extracellular mitochondria we have built to eventually identify a novel biomarker of sepsis-induced ARDS.