Willekens Frans L A, Werre Jan M, Kruijt J Kar, Roerdinkholder-Stoelwinder Bregt, Groenen-Döpp Yvonne A M, van den Bos Annegeet G, Bosman Giel J C G M, van Berkel Theo J C
Department of Clinical Chemistry, Rijnstate Hospital, Arnhem, The Netherlands.
Blood. 2005 Mar 1;105(5):2141-5. doi: 10.1182/blood-2004-04-1578. Epub 2004 Nov 18.
Previous studies have shown that during the lifespan of red blood cells (RBCs) 20% of hemoglobin is lost by shedding of hemoglobin-containing vesicles. However, the fate of these vesicles is unknown. To study this fate we used a rat model, after having established that rat RBCs lose hemoglobin in the same way as human RBCs, and that RBC-derived vesicles are preferentially labeled by Na2(51) CrO4. Such labeled vesicles were injected into recipient rats. Within 5 minutes, 80% of the radioactivity was cleared from the circulation with a concomitant uptake by the liver of 55% of the injected dose. After 30 minutes, Kupffer cells contained considerable amounts of hemoglobin and were shown to be responsible for 92% of the liver uptake. Vesicle clearance from the blood as well as liver uptake were significantly inhibited by preinjection of the scavenger-receptor ligands polyinosinic acid and phosphatidylserine. We conclude that in rats Kupffer cells rapidly remove RBC-derived vesicles from the circulation, mainly by scavenger receptors. The same mechanism is likely to be responsible for the elimination of human RBC vesicles, thereby constituting an important pathway for the breakdown of RBCs in humans.
先前的研究表明，在红细胞（RBC）的生命周期中，20%的血红蛋白通过含血红蛋白囊泡的脱落而丢失。然而，这些囊泡的命运尚不清楚。为了研究这种命运，我们使用了大鼠模型，此前已确定大鼠红细胞以与人类红细胞相同的方式丢失血红蛋白，并且红细胞衍生的囊泡优先被Na2(51)CrO4标记。将这种标记的囊泡注射到受体大鼠体内。5分钟内，80%的放射性物质从循环中清除，同时肝脏摄取了55%的注射剂量。30分钟后，库普弗细胞含有大量血红蛋白，并且显示其负责肝脏摄取的92%。预先注射清道夫受体配体多聚肌苷酸和磷脂酰丝氨酸可显著抑制囊泡从血液中的清除以及肝脏的摄取。我们得出结论，在大鼠中，库普弗细胞主要通过清道夫受体迅速从循环中清除红细胞衍生的囊泡。同样的机制可能负责清除人类红细胞囊泡，从而构成人类红细胞分解的重要途径。
