Acute pancreatitis promotes the generation of two different exosome populations

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.

The Role of MicroRNAs (miRNA 155, miRNA-146b) and Procalcitonin as Novel Markers for the Diagnosis of Spontaneous Bacterial Peritonitis

“…This goes in agreement with the findings of a study by Lutz et al, 2017, who found that miR-155 was significantly upregulated during spontaneous bacterial peritonitis when compared to ascites patients without spontaneous bacterial peritonitis infection [14]. Moreover, Jiménez-Alesanco et al 2019, initiated a study aimed to specify the different types of exosomes released by the pancreas to the pancreatitis-associated ascitic fluid as well as those circulating in plasma in an experimental model of acute pancreatitis in rats. They reported that two different populations of exosomes are generated with relevant differences in cell distribution, protein, and microRNA.…”

Association of plasma exosomes with severity of organ failure and mortality in patients with sepsis

“…Furthermore, exosomes possess the ability as a cell‐to‐cell communicator, triggering changes in broad spectrum of physiological and pathological processes in the acceptor cells. Previous studies demonstrated that exosomes are implicated in the development of organ dysfunction through cell‐to‐cell communication or organ crosstalk in sepsis 34‐37 . This finding suggests that exosomes may play a role in organ failure and sepsis without evident changes in the level of specific contents.…”

Identification of Potential Serum Exosomal microRNAs Involved in Acinar-Ductal Metaplasia That is A Precursor of Pancreatic Cancer Associated with Chronic Pancreatitis

“…Acute pancreatitis plasma exosomes contained more pro-in ammatory miRNA than exosomes from plasma control [22]. Therefore, exosomal microRNAs (Exo-miRNAs) in the serum could be potential biomarkers for diagnosing CP.…”