SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages
SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages
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DOI：
10.1182/blood-2005-05-1896
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发表时间：
2006-01-01
期刊：
影响因子：
20.3
通讯作者：
Nojima, Y
中科院分区：
文献类型：
--
作者：
Ishikawa-Sekigami, T;Kaneko, Y;Nojima, Y
骨髓中产生的循环红细胞 (RBC) 的寿命取决于其通过脾巨噬细胞的吞噬作用的消除。然而，调节红细胞消除的机制仍不清楚。表面糖蛋白 SHIPS-1 是免疫球蛋白超家族的成员，在巨噬细胞中含量丰富。我们现在已经使用表达缺乏大部分细胞质区域的 SHIPS-1 突变体的小鼠检查了红细胞周转的调节。突变小鼠表现出轻度贫血以及以红髓扩张为特征的脾肿大。突变小鼠脾脏中的红系前体细胞和循环网织红细胞的数量也有所增加。相反，这些动物中循环红细胞的半衰期缩短，并且注射的调理红细胞从外周循环中的清除率随着它们掺入脾巨噬细胞而增加。与野生型巨噬细胞观察到的相比，体外突变小鼠脾巨噬细胞对调理红细胞的吞噬作用也有所增加。这些结果表明SHPS-1负向调节脾巨噬细胞对红细胞的吞噬作用，从而决定单个红细胞的寿命和循环红细胞的数量。
The lifespan of circulating red blood cells (RBCs) produced in bone marrow is determined by their elimination through phagocytosis by splenic macrophages. The mechanism by which RBC elimination is regulated has remained unclear, however. The surface glycoprotein SHIPS-1, a member of the immunoglobulin superfamily, is abundant in macrophages. We have now examined the regulation of RBC turnover with the use of mice that express a mutant form of SHIPS-1 lacking most of its cytoplasmic region. The mutant mice manifested mild anemia as well as splenomegaly characterized by expansion of the red pulp. The numbers of erythroid precursor cells in the spleen and of circulating reticulocytes were also increased in the mutant mice. In contrast, the half-life of circulating RBCs was reduced in these animals, and the rate of clearance of injected opsonized RBCs from the peripheral circulation was increased in association with their incorporation into splenic macrophages. Phagocytosis of opsonized RBCs by splenic macrophages from mutant mice in vitro was also increased compared with that observed with wildtype macrophages. These results suggest that SHPS-1 negatively regulates the phagocytosis of RBCs by splenic macrophages, thereby determining both the lifespan of individual RBCs and the number of circulating erythrocytes.