title: Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Hematology-Oncology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ramos
authors.forename: Carla
authors.initials: C
authors.lastname: Casu
authors.forename: Sara
authors.initials: S
authors.lastname: Gardenghi
authors.forename: Laura
authors.initials: L
authors.lastname: Breda
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Crielaard
authors.forename: Ella
authors.initials: E
authors.lastname: Guy
authors.forename: Maria Franca
authors.initials: MF
authors.lastname: Marongiu
authors.forename: Ritama
authors.initials: R
authors.lastname: Gupta
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Wahab
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Saghi
authors.initials: S
authors.lastname: Ghaffari
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grady
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Giardina
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
mesh_terms: D000818:Animals; D004002:Clodronic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D004906:Erythrocyte Count; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011087:Polycythemia Vera / Q000503:physiopathology*; D012156:Reticulocytes / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology; D017086:beta-Thalassemia / Q000503:physiopathology*
chemical_list: D006454:Hemoglobins; D004002:Clodronic Acid