Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Erythrocytes of Nonalcoholic Steatohepatitis Patients Contain Decreased Arginase-1 and Thrombospondin-1, and Increased Phosphatidylethanolamine Levels

Version 1 : Received: 14 April 2023 / Approved: 17 April 2023 / Online: 17 April 2023 (04:22:12 CEST)

How to cite: Papadopoulos, C.; Mimidis, K.; Tentes, I.; Anagnostopoulos, K. Erythrocytes of Nonalcoholic Steatohepatitis Patients Contain Decreased Arginase-1 and Thrombospondin-1, and Increased Phosphatidylethanolamine Levels. Preprints 2023, 2023040397. https://doi.org/10.20944/preprints202304.0397.v1 Papadopoulos, C.; Mimidis, K.; Tentes, I.; Anagnostopoulos, K. Erythrocytes of Nonalcoholic Steatohepatitis Patients Contain Decreased Arginase-1 and Thrombospondin-1, and Increased Phosphatidylethanolamine Levels. Preprints 2023, 2023040397. https://doi.org/10.20944/preprints202304.0397.v1

Abstract

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Keywords

erythrocyte; non alcoholic steatohepatitis; immunometabolism; thrombospondin-1; arginase-1; phosphatidylethanolamine; metabolic inflammation 

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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