Abstract

The HSP-Accessorized Exosome: Presence in States of Danger, Disease, and Disruption

Michael Graner, Professor, University of Colorado Anschutz School of Medicine

Heat shock proteins (HSPs) function as chaperones under both normal and pathologic conditions. As chaperones they assist in protein folding, in holding protein complexes for current or future activation, and in the degradation of senescent proteins for recycling of components and display for immune surveillance. During stressful situations, HSP quantities and/or activities are increased as cells and tissues seek protection from insults. On occasion, these insults can result in the cell surface display of HSPs, which can then lead to the surface display of HSPs on exosomes, membrane-enclosed vesicles released extracellularly after passage thru the endosomal system. HSPs present on the cell surface or in the extracellular space are regarded as “danger signals” in an ancient biologic paradigm. HSP-accessorized exosomes may act as “danger boli”, carrying not only the HSPs, but hundreds of components of the stressed parental cell, capable of prompting immune responses, or possibly immune suppression, depending on the status of the recipient cell. Here we show that exosomes from the blood of patients suffering from neurologic maladies (cancer, brain injury, multiple sclerosis) are precipitated by peptides designed to bind HSPs. The metabolome of such exosomes is distinct from that of blood exosomes from healthy donors. Such HSP-accessorized exosomes possess inflammatory properties and may serve as biomarkers in a “liquid biopsy” setting.