116. The functional role of exosome associated extracellular heat shock protein 72 following exposure to acute stress

Abstract

One component of the adaptive stress response is that innate immunity is primed by circulating endogenous danger associated molecular patterns (DAMPs). Extracellular heat shock protein 72 (eHsp72) is a DAMP that is upregulated intracellularly after acute stress, but its mechanism of release is unknown. Previous in vitro studies have demonstrated the presence of Hsp72 on extracellular vesicles known as exosomes, which are biologically active vesicles secreted from all known cells in the body. We hypothesize that stress-evoked eHsp72 is released into the blood via an exosome pathway and that these exosomes are a critical component of stress-enhanced immunity. Male Fisher 344 rats (8/group) were subjected to tail shock stress or no stress, and exosome isolation from plasma was verified by size (EM and Nanosight) and common exosome markers (acetylcholinesterase, CD63, and Rab5b). We report that exposure to an acute stressor increases exosome expression of eHsp72, but not other stress-inducible proteins (IL-1β and IL-6). Additionally, exosomes from stressed, but not control, rats facilitates in vivo bactericidal inflammatory response ( p < 0.05) and an in vitro LPS-evoked inflammatory responses ( p < 0.05). These data suggest that exposure to stress can alter the proteomic composition of circulating exosomes, thereby enhancing the innate immune response.