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Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia

2013; Nature Portfolio; Volume: 19; Issue: 4 Linguagem: Inglês

10.1038/nm.3126

1546-170X

Pedro Luiz Ramos, Carla Casu, Sara Gardenghi, Laura Breda, Bart J. Crielaard, Ella Guy, Maria Franca Marongiu, Ritama Gupta, Ross L. Levine, Omar Abdel‐Wahab, Benjamin L. Ebert, Nico van Rooijen, Saghi Ghaffari, Robert W. Grady, Patricia J. Giardina, Stefano Rivella,

Erythrocyte Function and Pathophysiology

Ramos et al. report a crucial role for macrophages in erythroblast development in mice. Under conditions that induce new red blood cell formation, macrophage depletion impaired red blood cell recovery. Conversely, macrophage depletion normalized red blood cell counts in mouse models of polycythemia vera and ®-thalassemia, pointing to a potential new therapeutic strategy for these diseases. Findings similar to these are reported in an accompanying paper by Chow et al. Regulation of erythropoiesis is achieved by the integration of distinct signals. Among them, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages to physiological and pathological conditions of enhanced erythropoiesis. We used mouse models of induced anemia, polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively to recovery from induced anemia, as well as the pathological progression of polycythemia vera and β-thalassemia, by modulating erythroid proliferation and differentiation. We validated these observations in primary human cultures, showing a direct impact of macrophages on the proliferation and enucleation of erythroblasts from healthy individuals and patients with polycythemia vera or β-thalassemia. The contribution of macrophages to stress and pathological erythropoiesis, which we have termed stress erythropoiesis macrophage-supporting activity, may have therapeutic implications.