红浆
溶血
脾脏
白浆
亨氏机构
红细胞
生物
细胞生物学
血红蛋白
边缘地带
球形红细胞增多
免疫学
生物化学
化学
抗体
脾切除术
B细胞
作者
T R L Klei,Jill Dalimot,Benjamin Nota,Martijn Veldthuis,Frederik P. J. Mul,Timo Rademakers,Mark Hoogenboezem,Sietse Q. Nagelkerke,Wilfred F. J. van IJcken,Edwin Oole,Pia Svendsen,Søren K. Moestrup,Floris P.J. van Alphen,Alexander B. Meijer,Taco W. Kuijpers,Rob van Zwieten,Robin van Bruggen
出处
期刊:Blood
[American Society of Hematology]
日期:2020-08-10
被引量:19
标识
DOI:10.1182/blood.2020005351
摘要
Red pulp macrophages of the spleen mediate turnover of billions of senescent erythrocytes per day. However, the molecular mechanisms involved in sequestration of senescent erythrocytes, their recognition and their subsequent degradation by red pulp macrophages remain unclear. In this study we provide evidence that the splenic environment is of substantial importance in facilitating erythrocyte turnover through induction of hemolysis. Upon isolating human spleen red pulp macrophages we noted a substantial lack of macrophages that were in the process of phagocytosing intact erythrocytes. Detailed characterization of erythrocyte and macrophage subpopulations from human spleen tissue led to the identification of erythrocytes that are devoid of hemoglobin, so-called erythrocyte ghosts. By in vivo imaging and transfusion experiments we further confirmed that senescent erythrocytes that are retained in the spleen are subject to hemolysis. Additionally, we show that erythrocyte adhesion molecules, which are specifically activated on aged erythrocytes, cause senescent erythrocytes to interact with extracellular matrix proteins that are exposed within the splenic architecture. Such adhesion molecule-driven retention of senescent erythrocytes, under low shear conditions, was found to result in steady shrinkage of the cell and ultimately resulted in hemolysis. In contrast to intact senescent erythrocytes, the remnant erythrocyte ghost shells were prone to recognition and breakdown by red pulp macrophages. These data identify hemolysis as a key event in the turnover of senescent erythrocytes, which alters our current understanding of how erythrocyte degradation is regulated.
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