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, Timo K van den Berg

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)5223-9
Number of pages7
JournalBlood
Volume109
Issue number12
DOIs
Publication statusPublished - 15 Jun 2007

Cite this

Fabriek, B. O., Polfliet, M. M. J., Vloet, R. P. M., van der Schors, R. C., Ligtenberg, A. J. M., Weaver, L. K., ... van den Berg, T. K. (2007). The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor. Blood, 109(12), 5223-9. https://doi.org/10.1182/blood-2006-08-036467
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. / The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor. In: Blood. 2007 ; Vol. 109, No. 12. pp. 5223-9.
@article{307f42fa47e94947bbe1fa605fee9c19,
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.",
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Fabriek, BO, Polfliet, MMJ, Vloet, RPM, van der Schors, RC, Ligtenberg, AJM, Weaver, LK, Geest, C, Matsuno, K, Moestrup, SK, Dijkstra, CD & van den Berg, TK 2007, 'The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor' Blood, vol. 109, no. 12, pp. 5223-9. https://doi.org/10.1182/blood-2006-08-036467

The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor. / 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.

In: Blood, Vol. 109, No. 12, 15.06.2007, p. 5223-9.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor

AU - Fabriek, Babs O

AU - Polfliet, Machteld M J

AU - Vloet, Rianka P M

AU - van der Schors, Roel C

AU - Ligtenberg, Antoon J M

AU - Weaver, Lehn K

AU - Geest, Christiaan

AU - Matsuno, Kenjiro

AU - Moestrup, Søren K

AU - Dijkstra, Christien D

AU - van den Berg, Timo K

PY - 2007/6/15

Y1 - 2007/6/15

N2 - 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.

AB - 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.

KW - Amino Acid Motifs

KW - Animals

KW - Antigens, CD/physiology

KW - Antigens, Differentiation, Myelomonocytic/physiology

KW - Binding Sites

KW - Bone Marrow Cells

KW - Cell Adhesion

KW - Cell Proliferation

KW - Erythroblasts/cytology

KW - Erythropoiesis

KW - Macrophages/chemistry

KW - Membrane Glycoproteins

KW - Membrane Proteins

KW - Platelet Glycoprotein GPIb-IX Complex

KW - Rats

KW - Receptors, Cell Surface/physiology

U2 - 10.1182/blood-2006-08-036467

DO - 10.1182/blood-2006-08-036467

M3 - Article

VL - 109

SP - 5223

EP - 5229

JO - Blood

JF - Blood

SN - 0006-4971

IS - 12

ER -

Fabriek BO, Polfliet MMJ, Vloet RPM, van der Schors RC, Ligtenberg AJM, Weaver LK et al. The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor. Blood. 2007 Jun 15;109(12):5223-9. https://doi.org/10.1182/blood-2006-08-036467