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Hematopoiesis
Glucocorticoids induce differentiation of mono- cytes towards macrophages that share func- tional and phenotypical aspects with erythroblastic island macrophages
Esther Heideveld,1 Lea A. Hampton-O’Neil,2 Stephen J. Cross,3
Floris P.J. van Alphen,4 Maartje van den Biggelaar,4,5 Ashley M. Toye2,6,7 and Emile van den Akker1
1Sanquin Research, Department of Hematopoiesis, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands; 2Department of Biochemistry, School of Medical Sciences, Bristol, UK; 3Wolfson Bioimaging Facility, School of Medical Sciences, Bristol, UK; 4Sanquin Research, Department of Research Facilities, Amsterdam, the Netherlands; 5Sanquin Research, Department of Plasma Proteins, Amsterdam, the Netherlands 6Bristol Institute for Transfusion Sciences, NHS Blood and Transplant, Filton, Bristol, UK and 7National Institute for Health Research (NIHR) Blood and Transplant Research Unit in Red Blood Cell Products, University of Bristol, UK
ABSTRACT
The classical central macrophage found in erythroblastic islands plays an important role in erythroblast differentiation, prolifera- tion and enucleation in the bone marrow. Convenient human in vitro models to facilitate the study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance in vitro erythropoiesis by supporting hematopoietic stem and progenitor cell survival. Herein, we describe that these specific macrophages also support erythropoiesis. Human monocytes cultured in serum-free media supplemented with stem cell factor, erythropoietin, lipids and dexamethasone differentiate towards macrophages expressing CD16, CD163, CD169, CD206, CXCR4 and the phagocytic TAM-receptor family. Phenotypically, they resemble both human bone marrow and fetal liver resident macrophages. This dif- ferentiation is dependent on glucocorticoid receptor activation. Proteomic studies confirm that glucocorticoid receptor activation differ- entiates monocytes to anti-inflammatory tissue macrophages with a M2 phenotype, termed GC-macrophages. Proteins involved in migration, tissue residence and signal transduction/receptor activity are upregulated whilst lysosome and hydrolase activity GO-categories are downregulat- ed. Functionally, we demonstrate that GC-macrophages are highly mobile and can interact to form clusters with erythroid cells of all differ- entiation stages and phagocytose the expelled nuclei, recapitulating aspects of erythroblastic islands. In conclusion, glucocorticoid-directed monocyte differentiation to macrophages represents a convenient model system to study erythroid-macrophage interactions.
Introduction
In human bone marrow (BM) and fetal liver (FL), the production of erythrocytes through erythropoiesis occurs on erythroblastic islands.1,2 These erythroblastic islands consist of a central macrophage surrounded by erythroid cells at different stages of terminal differentiation and support proliferation, differentiation and phagocytose the extruded nuclei (or pyrenocytes) of erythroid cells.2-6 Chow et al. described that mouse CD169+ (SIGLEC1) BM resident macrophages display a dual role promoting erythropoiesis and retention of hematopoietic stem and progenitor cells (HSPC).7,8 Their absence leads to the mobilization of HSPC, reduced BM ery- thropoiesis and the inability to properly respond to anemia.7-10 It is, however, unclear whether CD169 identifies different macrophage populations or indicates an intrinsic dual role for the same tissue macrophage. FL macrophages that are unable to interact with erythroblasts due to disruption of the retinoblastoma tumor sup-
Ferrata Storti Foundation
Haematologica 2018 Volume 103(3):395-405
Correspondence:
e.vandenakker@sanquin.nl
Received: August 22, 2017. Accepted: December 27, 2017. Pre-published: December 28, 2017.
doi:10.3324/haematol.2017.179341
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/3/395
©2018 Ferrata Storti Foundation
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