Fabriek Babs O, Polfliet Machteld M J, Vloet Rianka P M, van der Schors Roel C, Ligtenberg Antoon J M, Weaver Lehn K, Geest Christiaan, Matsuno Kenjiro, Moestrup Søren K, Dijkstra Christien D, van den Berg Timo K
Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
Blood. 2007 Jun 15;109(12):5223-9. doi: 10.1182/blood-2006-08-036467. Epub 2007 Mar 12.
Erythropoiesis occurs in erythroblastic islands, where developing erythroblasts closely interact with macrophages. The adhesion molecules that govern macrophage-erythroblast contact have only been partially defined. Our previous work has implicated the rat ED2 antigen, which is highly expressed on the surface of macrophages in erythroblastic islands, in erythroblast binding. In particular, the monoclonal antibody ED2 was found to inhibit erythroblast binding to bone marrow macrophages. Here, we identify the ED2 antigen as the rat CD163 surface glycoprotein, a member of the group B scavenger receptor cysteine-rich (SRCR) family that has previously been shown to function as a receptor for hemoglobin-haptoglobin (Hb-Hp) complexes and is believed to contribute to the clearance of free hemoglobin. CD163 transfectants and recombinant protein containing the extracellular domain of CD163 supported the adhesion of erythroblastic cells. Furthermore, we identified a 13-amino acid motif (CD163p2) corresponding to a putative interaction site within the second scavenger receptor domain of CD163 that could mediate erythroblast binding. Finally, CD163p2 promoted erythroid expansion in vitro, suggesting that it enhanced erythroid proliferation and/or survival, but did not affect differentiation. These findings identify CD163 on macrophages as an adhesion receptor for erythroblasts in erythroblastic islands, and suggest a regulatory role for CD163 during erythropoiesis.
红细胞生成发生于成红细胞岛，在此处发育中的成红细胞与巨噬细胞密切相互作用。调控巨噬细胞 - 成红细胞接触的黏附分子仅得到了部分界定。我们之前的研究表明，大鼠ED2抗原在成红细胞岛的巨噬细胞表面高度表达，参与成红细胞的黏附。特别地，发现单克隆抗体ED2可抑制成红细胞与骨髓巨噬细胞的黏附。在此，我们确定ED2抗原为大鼠CD163表面糖蛋白，它是富含半胱氨酸的B类清道夫受体（SRCR）家族的成员，先前已证明其作为血红蛋白 - 触珠蛋白（Hb - Hp）复合物的受体发挥作用，并且被认为有助于清除游离血红蛋白。CD163转染细胞以及含有CD163胞外域的重组蛋白支持成红细胞样细胞的黏附。此外，我们鉴定出一个13个氨基酸的基序（CD163p2），它对应于CD163第二个清道夫受体结构域内的一个假定相互作用位点，该位点可介导成红细胞的黏附。最后，CD163p2在体外促进红系扩增，表明它增强了红系增殖和/或存活，但不影响分化。这些发现确定巨噬细胞上的CD163为成红细胞岛中成红细胞的黏附受体，并提示CD163在红细胞生成过程中具有调节作用。
