Abstract
Exosomes are small extracellular vesicles that act as intercellular messengers. Previous studies revealed that, during acute pancreatitis, circulating exosomes could reach the alveolar compartment and activate macrophages. However, proteomic analysis suggested that the most likely origin of these exosomes could be the liver instead of the pancreas. The present study aimed to characterize the exosomes released by pancreas to pancreatitis-associated ascitic fluid (PAAF) as well as those circulating in plasma in an experimental model of taurocholate-induced acute pancreatitis in rats. We provide evidence that during acute pancreatitis two different populations of exosomes are generated with relevant differences in cell distribution, protein and microRNA content as well as different implications in their physiological effects. During pancreatitis plasma exosomes, but not PAAF exosomes, are enriched in the inflammatory miR-155 and show low levels of miR-21 and miR-122. Mass spectrometry-based proteomic analysis showed that PAAF exosomes contains 10–30 fold higher loading of histones and ribosomal proteins compared to plasma exosomes. Finally, plasma exosomes have higher pro-inflammatory activity on macrophages than PAAF exosomes. These results confirm the generation of two different populations of exosomes during acute pancreatitis. Deep understanding of their specific functions will be necessary to use them as therapeutic targets at different stages of the disease.
Highlights
Exosomes are small extracellular vesicles that act as intercellular messengers
Extracellular vesicles isolated from both plasma and pancreatitis-associated ascitic fluid (PAAF) were morphologically characterized by transmission electron microscopy (TEM)
In the case of acute pancreatitis, the role of exosomes in activation of macrophages has been previously reported in vitro, by evaluating the role of exosomes released by stimulated pancreatic acinar cells on macrophages[10], as well as in vivo, by using the taurocholate-induced pancreatitis model in rats[9]
Summary
Exosomes are small extracellular vesicles that act as intercellular messengers. Previous studies revealed that, during acute pancreatitis, circulating exosomes could reach the alveolar compartment and activate macrophages. From the first description of acute pancreatitis in 1895, it has been evaluated a number of mediators potentially involved in the progression of the disease from the local pancreatic damage to systemic inflammation Along these years, hydrolytic enzymes, hormones, oxygen free radicals, cytokines, bioactive lipids and virtually any known molecule that can be suspected to have a role in the process, have been analyzed[4,5,6,7]. The proteomic analysis of exosomes purified from plasma of rats with acute pancreatitis did not showed the presence of pancreatic proteins By contrast, it revealed a significant amount of proteins of supposedly hepatic origin, including apolipoproteins, mannose-binding protein or hemoglobin subunits. In addition to remarkable differences in protein and micro-RNA (mi-R) content, these exosomes showed significant differences in body distribution as well as in their physiopathological roles
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