The Microenvironment in an Experimental Model of Acute Pancreatitis Can Modify the Formation of the Protein Corona of sEVs, with Implications on Their Biological Function.

Abstract

A considerable number of the physiological functions of extracellular vesicles are conditioned by the protein corona attached to their surface. The composition of this corona is initially defined during their intracellular synthesis, but it can be subsequently modified by interactions with the microenvironment. Here, we evaluated how the corona of small extracellular vesicles exposed to the inflammatory environment generated in acute pancreatitis is modified and what functional changes occur as a result of these modifications. Small extracellular vesicles obtained from a pancreatic cell line were incubated with the ascitic fluid generated in experimental acute pancreatitis in rats. Using proteomic techniques, we detected the appearance of new proteins and an increase the uptake of extracellular vesicles by certain cell types and the response induced in inflammatory cells. The inhibition of different pattern recognition receptors reversed this activation, indicating that some of these effects could be due to binding of damage-associated molecular patterns to the corona. All of this indicates that in pathologies such as acute pancreatitis, characterized by an inflammatory response and intense tissue damage, the microenvironment substantially influences the corona of extracellular vesicles, thus altering their behavior and enhancing their inflammatory activity.