Angiotensin II stimulates proliferation of normal early erythroid progenitors
Angiotensin II stimulates proliferation of normal early erythroid progenitors
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DOI：
10.1172/jci119769
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发表时间：
1997-11-01
影响因子：
15.9
通讯作者：
Prchal, JT
中科院分区：
文献类型：
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作者：
Mrug, M;Stopka, T;Prchal, JT
血管紧张素II在几种体外模型中发挥促有丝分裂作用，但对红系祖细胞的直接作用尚未被证实。血管紧张素转换酶抑制剂和血管紧张素II 1型受体（AT（1））拮抗剂氯沙坦可改善移植后红细胞增多，而不改变血清促红细胞生成素水平。我们研究了红系分化和血管紧张素II对红系祖细胞增殖的影响，通过在有利于红系前体细胞生长的无血清液体培养基中培养CD 34+造血祖细胞。每三天收集一次细胞的等分试样，并用于RNA制备。AT（1）mRNA在培养6d后开始表达。在这些相同的样品中，还检测到红细胞特异性mRNA（促红细胞生成素受体）。Western blotting检测到AT（1）蛋白存在于7日龄的红系集落中。使用CD 34+细胞液体培养物在第6-9天用血管紧张素II孵育红系前体。孵育后，将细胞转移至半固体培养基中，并与促红细胞生成素一起培养。血管紧张素II促进早期红系祖细胞增殖，定义为红系集落的爆发形成单位数量增加，氯沙坦完全消除了血管紧张素II的这种刺激作用。此外，我们观察到移植后红细胞增多症患者外周血中红系祖细胞数量增加。因此，血管紧张素II激活AT（1）可增强体外促红细胞生成素刺激的红系细胞增殖。血管紧张素II/AT（1）通路的假定缺陷可能导致移植后红细胞增多症的发病机制。
Angiotensin II exerts a mitogenic effect in several in vitro models, but a direct effect on erythroid progenitors has not been documented. Angiotensin-converting enzyme inhibitors and losartan, an angiotensin II type 1 receptor (AT(1)) antagonist, ameliorate posttransplant erythrocytosis, without altering serum erythropoietin levels. We studied erythroid differentiation and the effect of angiotensin II on proliferation of erythroid progenitors by culturing CD34+ hematopoietic progenitor cells in liquid serum-free medium favoring growth of erythroid precursors. Aliquots of cells were collected every third day, and were used for RNA preparation. AT(1) mRNA was detected after 6 d. In these same samples, erythroid-specific mRNA (erythropoietin receptor) was also detected. AT(1) protein was detected in 7-d-old burst-forming units-erythroid colonies by Western blotting. The CD34+ cell liquid cultures were used to incubate erythroid precursors with angiotensin II from days 6-9. After incubation, cells were transferred to semisolid medium and cultured with erythropoietin. Angiotensin II increased proliferation of early erythroid progenitors, defined as increased numbers of burst-forming units-erythroid colonies, Losartan completely abolished this stimulatory effect of angiotensin II, Moreover, we observed increased numbers of erythroid progenitors in the peripheral blood of posttransplant erythrocytosis patients. Thus, activation of AT(1) with angiotensin II enhances erythropoietin-stimulated erythroid proliferation in vitro. A putative defect in the angiotensin II/AT(1) pathway may contribute to the pathogenesis of posttransplant erythrocytosis.