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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5074-5075.
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HEMATOPOIESIS
Comment on Fabriek et al, page 5223
Scavenger receptor helps erythroblasts stay on island
Mark J. Koury
1 VA TENNESSEE VALLEY HEALTHCARE SYSTEM
In this issue of Blood, Fabriek and colleagues identify CD163, a scavenger receptor expressed on macrophages, as a mediator of erythroblast-macrophage adhesion in erythroblastic islands. Given that CD163 is also the macrophage receptor for circulating hemoglobin-haptoglobin complexes and its expression varies in response to inflammation, it may play a role in feedback regulation of erythropoiesis related to iron recycling and inflammation.
As part of interactions between stromal and hematopoietic cells, late-stage erythropoiesis has a morphologically recognized, functional unit termed the erythroblastic island, which is composed of a central, stromal macrophage surrounded by adherent erythroblasts.1 Erythroblastic islands are found in extramedullary sites such as the spleen during erythropoietic stress, as well as normal erythropoietic sites such as fetal liver and adult bone marrow. These islands support erythroid progenitors and precursor cells from the stages of erythropoietin dependence (erythroid colony-forming units [CFU-Es], and proerythroblasts) through enucleation and the formation of immature reticulocytes. Interaction with the central macrophages enhances erythroblast survival, proliferation, and differentiation during these terminal stages of erythropoiesis. Central macrophages also phagocytose nuclei extruded from erythroblasts during the formation of reticulocytes. Four specific proteins on the surface of macrophages have been previously shown to mediate the adherence of erythroblasts.1 These previously identified macrophage proteins and their binding partners on erythroblasts include: vascular cell adhesion molecule-1 (VCAM-1), which binds to  4ß1 integrin (VLA-4); V integrin (eg, Vß1), which binds interstitial cell adhesion molecule-4 (ICAM-4); erythroblast-macrophage protein (EMP), which is thought to interact with itself; and sialoadhesin (CD169; Siglec-1), which binds sialated glycoproteins. Now, CD163 can be added to this group of macrophage proteins that mediate erythroblast adhesion. Antibodies and/or blocking peptides to each macrophage adhesion protein or its respective erythroblast binding partner have disrupted, to varying amounts, the macrophage–erythroblast adherence. These disruptions of adherence raise the possibilities that the adhesion proteins may associate in complexes, cooperate in their expressions or activities, or function at different times during the course of late erythroid differentiation.
CD163 is a member of the scavenger receptor cysteine–rich (SRCR) family of transmembrane glycoproteins that are commonly found on cells of the immune system.2 Although its binding partner on the erythroblast has not yet been identified, Fabriek and colleagues have demonstrated that the site in the extracellular portion of macrophage CD163 that binds the erythroblast is different than the binding site for the hemoglobin-haptoglobin complex. Macrophage binding and endocytosis of hemoglobin-haptoglobin complexes remove and degrade plasma hemoglobin, a potentially toxic product of intravascular hemolysis. The subsequent degradation of the heme and recycling of its iron by macrophages is important for the production of new erythrocytes in these hemolytic anemias. CD163 expression, which is restricted to the monocyte/macrophage lineage, is enhanced by anti-inflammatory stimuli such as glucocorticoids or interleukin-10 and is suppressed by proinflammatory stimuli such as interferon- and tissue necrosis factor-.2 Thus, the newly described function of CD163 as a mediator of macrophage-erythroblast adhesion in erythroblastic islands may provide insight into the expansion of erythropoiesis in hemolysis as well as the suppression of erythropoiesis associated with inflammation.
Footnotes
Conflict-of-interest disclosure: The author declares no competing financial interests. 
REFERENCES
- Chasis JA. Erythroblastic islands: specialized microenvironmental niches for erythropoiesis. Curr Opin Hematol 2006; 13:137–141.[Medline]
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- Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology 2005; 210:153–160.[CrossRef][Medline]
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Related Article in Blood Online:
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The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor
- Babs O. Fabriek, Machteld M. J. Polfliet, Rianka P. M. Vloet, Roel C. van der Schors, Antoon J. M. Ligtenberg, Lehn K. Weaver, Christiaan Geest, Kenjiro Matsuno, Søren K. Moestrup, Christien D. Dijkstra, and Timo K. van den Berg
Blood 2007 109: 5223-5229.
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