title: The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor.
abstract: 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.
authors.affiliation: Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
authors.forename: Babs O
authors.initials: BO
authors.lastname: Fabriek
authors.forename: Machteld M J
authors.initials: MM
authors.lastname: Polfliet
authors.forename: Rianka P M
authors.initials: RP
authors.lastname: Vloet
authors.forename: Roel C
authors.initials: RC
authors.lastname: van der Schors
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: Ligtenberg
authors.forename: Lehn K
authors.initials: LK
authors.lastname: Weaver
authors.forename: Christiaan
authors.initials: C
authors.lastname: Geest
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsuno
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: Christien D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: Timo K
authors.initials: TK
authors.lastname: van den Berg
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D001665:Binding Sites; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D049109:Cell Proliferation; D004900:Erythroblasts / Q000166:cytology*; D004920:Erythropoiesis; D008264:Macrophages / Q000737:chemistry* / Q000166:cytology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D011956:Receptors, Cell Surface; C094990:adhesion receptor