Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
Por:
Carrascal, M, Areny-Balaguero, A, de-Madaria, E, Cardenas-Jaen, K, Garcia-Rayado, G, Rivera, R, Mateos, R, Pascual-Moreno, I, Gironella, M, Abian, J and Closa, D
Publicada:
1 ene 2022
Ahead of Print:
1 oct 2021
Resumen:
As acute pancreatitis progresses to the severe form, a life-threatening systemic inflammation is triggered. Although the mechanisms involved in this process are not yet well understood, it has been proposed that circulating exosomes may be involved in the progression of inflammation from the pancreas to distant organs. Here, the inflammatory capacity and protein profile of plasma exosomes obtained during the first 24 h of hospitalization of patients diagnosed with acute pancreatitis were characterized and compared with the final severity of the disease. We found that the final severity of the disease strongly correlates with the inflammatory capacity of exosomes in the early stages of acute pancreatitis. Exosomes isolated from patients with mild pancreatitis had no effect on macrophages, while exosomes isolated from patients with severe pancreatitis triggered NF kappa B activation, TNF alpha and IL1 beta expression, and free radical generation. To delve deeper into the mechanism involved, we performed a proteomic analysis of the different exosomes that allowed us to identify different groups of proteins whose concentration was also correlated with the clinical classification of pancreatitis. In particular, an increase in the amount of S100A8 and S100A9 carried by exosomes of severe pancreatitis suggests that the mechanism of action of exosomes is mediated by the effect of these proteins on NADPH oxidase. This enzyme is activated by S100A8/S100A9, thus generating free radicals and promoting an inflammatory response. Along these lines, we observed that inhibition of this enzyme abolished all the pro-inflammatory effects of exosomes from severe pancreatitis. All this suggests that the systemic effects, and therefore the final severity of acute pancreatitis, are determined by the content of circulating exosomes generated in the early hours of the process. (c) 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Filiaciones:
Carrascal, M:
Inst Invest Biorned August Pi i Sunyer IDIBAPS, Biol & Environm Prote, Inst Invest Biomed Barcelona, Consejo Super Invest Cient IIBB CSIC, Barcelona, Spain
Areny-Balaguero, A:
Inst Invest Biorned August Pi i Sunyer IDIBAPS, Dept Expt Pathol, Inst Invest Biomed Barcelona, Consejo Super Invest Cient IIBB CSIC, Barcelona, Spain
:
Alicante Univ Gen Hosp, Alicante Inst Hlth & Biomed Res ISABIAL, Gastroenterol Dept, Alicante, Spain
:
Alicante Univ Gen Hosp, Alicante Inst Hlth & Biomed Res ISABIAL, Gastroenterol Dept, Alicante, Spain
Garcia-Rayado, G:
Univ Clin Hosp Lozano Blesa, Aragon Hlth Res Inst IIS Aragon, Serv Digest Dis, Zaragoza, Spain
Rivera, R:
Hosp Costa Sol Marbella, Gastroenterol Dept, Malaga, Spain
Mateos, R:
Univ Alcalo, Hosp Univ Ramon Y Cajal, Ctr Invest Biomed Red Enferrnedades Hepat & Diges, Inst Ramon Y Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Pascual-Moreno, I:
Univ Valencia, Hosp Clin Univ Valencia, Inst Invest Sanitaria Valencia INCLIVA, Dept Gastroenterol, Valencia, Spain
Gironella, M:
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Gastrointestinal & Pancreat Oncol, Hosp Clin Barcelona, Ctr Invest Biomed Red Enferrnedades Hepat & Diges, Barcelona, Spain
Abian, J:
Inst Invest Biorned August Pi i Sunyer IDIBAPS, Biol & Environm Prote, Inst Invest Biomed Barcelona, Consejo Super Invest Cient IIBB CSIC, Barcelona, Spain
Closa, D:
Inst Invest Biorned August Pi i Sunyer IDIBAPS, Dept Expt Pathol, Inst Invest Biomed Barcelona, Consejo Super Invest Cient IIBB CSIC, Barcelona, Spain
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