Direct Ingestion of Oxidized Red Blood Cells (Efferocytosis) by Hepatocytes.

Both hepatic iron accumulation and hemolysis have been identified as independent prognostic factor in alcohol-related liver disease (ALD); however, the mechanisms still remain poorly understood. We here demonstrate that hepatocytes are able to directly ingest aged and ethanol-primed red blood cells (RBCs), a process termed efferocytosis. Efferocytosis of RBCs was directly studied in vitro and observed by live microscopy for real-time visualization. RBCs pretreated with either CuSO As shown by live microscopy, oxidized RBCs, but not intact RBCs, are rapidly ingested by both Huh7 cells and murine primary hepatocytes within 10 minutes. In some cases, more than 10 RBCs were seen within hepatocytes, surrounding the nucleus. RBC efferocytosis also rapidly induces We here demonstrate that hepatocytes can directly ingest and degrade oxidized RBCs through efferocytosis, a process that can be also triggered by ethanol, heme and bilirubin. Our findings are highly suggestive for a novel mechanism of hepatic iron overload in ALD patients.

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© 2024 Zheng et al.

Déclaration de conflit d'intérêts

Dr Seddik Hammad reports grants from The Stiftung für Biomedizinische Alkoholforschung, the BMBF (German Federal Ministry of Education and Research) Project LiSyM (Grant PTJ-FKZ: 031L0043) and LiSyM-Cancer (Grant PTJ-FKZ: 031L0257A), outside the submitted work. The authors report no other conflicts of interest in this work.