Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia.
Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia.
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红细胞生成的调节是通过整合不同的信号来实现的。其中，巨噬细胞正在成为红细胞生成素的互补调节因子，特别是在应激条件下。我们研究了巨噬细胞对红细胞生成增强的生理和病理条件的贡献。我们利用小鼠模型诱导性贫血，真性红细胞增多症和β-地中海贫血，其中巨噬细胞化学耗尽。我们的数据表明，巨噬细胞通过调节红细胞增殖和分化，对诱导性贫血的恢复以及真性红细胞增多症和β-地中海贫血的病理进展起决定性作用。我们在原代人培养中验证了这些观察结果，显示巨噬细胞对健康个体和真性红细胞增多症或β-地中海贫血患者的红细胞增殖和去核具有关键的直接影响。总之，我们确定了一种新的机制，我们将其命名为“应激性红细胞生成巨噬细胞支持活性”（SEMA），它有助于这些疾病的病理生理学，并将在不久的将来具有重要的科学和治疗意义。
Regulation of erythropoiesis is achieved by integration of distinct signals. Among these, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages for physiological and pathological conditions of enhanced erythropoiesis. We utilized mouse models of induced anemia, Polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively for 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 critical direct impact of macrophages on proliferation and enucleation of erythroblasts from healthy individuals and Polycythemia vera or β-thalassemic patients. In summary, we identify a new mechanism that we named “Stress Erythropoiesis Macrophage-supporting Activity” (SEMA) that contributes to the pathophysiology of these disorders and will have critical scientific and therapeutic implications in the near future.