Hepatology (Baltimore, Md.) · 2014
Conjugated bilirubin triggers anemia by inducing erythrocyte death.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Lang Elisabeth, Gatidis Sergios, Freise Noemi F, Bock Hans, Kubitz Ralf, Lauermann Christian, Orth Hans Martin, Klindt Caroline, Schuier Maximilian, Keitel Verena, Reich Maria, Liu Guilai, Schmidt Sebastian, Xu Haifeng C, Qadri Syed M, Herebian Diran, Pandyra Aleksandra A, Mayatepek Ertan, Gulbins Erich, Lang Florian, Häussinger Dieter, Lang Karl S, Föller Michael, Lang Philipp A
Аннотация
UNLABELLED: 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 Ca(2+) 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.
CONCLUSION: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease.