Conjugated bilirubin triggers anemia by inducing erythrocyte death
| Autor: | Diran Herebian, Florian Lang, Verena Keitel, Haifeng C. Xu, Karl S. Lang, Erich Gulbins, Philipp A. Lang, Sergios Gatidis, Noemi F. Freise, Michael Föller, Dieter Häussinger, Caroline Klindt, Ralf Kubitz, Hans Martin Orth, Hans H. Bock, Aleksandra A. Pandyra, Ertan Mayatepek, Christian Lauermann, Sebastian Schmidt, M Reich, Maximilian Schuier, Elisabeth Lang, Syed M. Qadri, Guilai Liu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Programmed cell death Erythrocytes Bilirubin Anemia Medizin Biology Mice chemistry.chemical_compound Liver disease Phospholipid scrambling Reticulocyte Internal medicine medicine Animals Humans Aged Cell Death Hepatology Phosphatidylserine Middle Aged medicine.disease Healthy Volunteers Sphingomyelin Phosphodiesterase Autoimmune Cholestatic and Biliary Disease Endocrinology medicine.anatomical_structure chemistry Case-Control Studies Immunology Calcium Female Liver Failure |
| Zdroj: | Hepatology (Baltimore, Md.) |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.27338 |
| Popis: | Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284) |
| Databáze: | OpenAIRE |
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