Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia

被引:190
作者
Ramos, Pedro [1 ]
Casu, Carla [1 ]
Gardenghi, Sara [1 ]
Breda, Laura [1 ]
Crielaard, Bart J. [1 ]
Guy, Ella [1 ]
Marongiu, Maria Franca [1 ]
Gupta, Ritama [1 ]
Levine, Ross L. [2 ,3 ]
Abdel-Wahab, Omar [2 ,3 ]
Ebert, Benjamin L. [4 ]
Van Rooijen, Nico [5 ]
Ghaffari, Saghi [6 ]
Grady, Robert W. [1 ]
Giardina, Patricia J. [1 ]
Rivella, Stefano [1 ,7 ]
机构
[1] Weill Cornell Med Coll, Dept Pediat, Div Hematol Oncol, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, Human Oncol & Pathogenesis Program, New York, NY 10021 USA
[3] Weill Cornell Med Coll, New York, NY USA
[4] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA
[5] Vrije Univ Amsterdam, Dept Mol Cell Biol, Med Ctr, Amsterdam, Netherlands
[6] Mt Sinai Sch Med, Div Hematol Oncol, Dept Med, New York, NY USA
[7] Weill Cornell Med Coll, Dept Cell & Biol Dev, New York, NY USA
基金
美国国家卫生研究院;
关键词
TYROSINE KINASE JAK2; INEFFECTIVE ERYTHROPOIESIS; STRESS ERYTHROPOIESIS; MOUSE MODEL; DICHLOROMETHYLENE DIPHOSPHONATE; ERYTHROBLASTIC ISLANDS; IRON OVERLOAD; BONE-MARROW; CELLS; MUTATION;
D O I
10.1038/nm.3126
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-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 b-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 b-thalassemia. The contribution of macrophages to stress and pathological erythropoiesis, which we have termed stress erythropoiesis macrophage-supporting activity, may have therapeutic implications.
引用
收藏
页码:437 / +
页数:11
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