Effect of angiotensin II and angiotensin(1-7) on hematopoietic recovery after intravenous chemotherapy
Effect of angiotensin II and angiotensin(1-7) on hematopoietic recovery after intravenous chemotherapy
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DOI：
10.1007/s00280-002-0509-4
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发表时间：
2003-02-01
影响因子：
3
通讯作者：
diZerega, GS
中科院分区：
文献类型：
--
作者：
Rodgers, K;Xiong, SQ;diZerega, GS
目的：以往的研究表明，血管紧张素肽在体外可刺激造血祖细胞的增殖，促进致死性照射后的存活，加速白细胞(WBC)的恢复，即淋巴细胞、单核细胞、中性粒细胞和血小板。IRRA-后血液中形成元素水平的这些变化。这些变化被认为是由于血管紧张素肽的作用增加了包括髓系、红系和巨核细胞在内的骨髓祖细胞的数量。鉴于这些发现，评估了血管紧张素肽对化疗后恢复的影响。材料和方法：在小鼠模型上观察血管紧张素11(ALL)和血管紧张素(1-7)(A1-7)对小鼠静脉注射化疗药物后外周血中白细胞和血小板的恢复以及骨髓中髓系、红系和巨核系祖细胞数量以及血液中髓系祖细胞数量的影响。结果：在最初的研究中，在静脉注射5-氟尿嘧啶(5FU)的前2天或2天后，每天皮下注射10或100毫克/公斤的ALL可加速WBC的恢复(在7至14天内恢复到基线水平)。此外，与先前的观察一致，全身应用血管紧张素肽后，骨髓和血液中的髓系祖细胞数量增加。在随后的研究中，A(1-7)和ALL在化疗后对造血恢复的影响方面具有可比性。每天服用AII和A(1-7)均可增加外周血中的血小板数量以及骨髓中的髓系、红系和巨核系祖细胞。由于5FU不是一种干细胞毒素，这些研究在静脉注射环磷酰胺之前或之后开始使用A(1-7)重复进行。环磷酰胺前应用A(1-7)后，外周血和骨髓中外周血和骨髓中的WBC数量和髓系祖细胞数量均增加，从第14天开始循环WBC数先升高后下降。结论：这些发现提示血管紧张素肽促进化疗后多细胞系的造血恢复，可能是通过增加早期造血祖细胞的数量。
Purpose: Previous studies have shown that angiotensin peptides stimulate the proliferation of hematopoietic progenitors in vitro, promote survival after exposure to lethal irradiation as well as accelerate the recovery of white blood cells (WBC), i.e., lymphocytes, monocytes and neutrophils, and platelets. These changes in the level of formed elements in the blood after irra-. diation was thought to be due to increases in the numbers of bone marrow progenitors including myeloid, erythroid and megakaryocyte progenitors by the action of angiotensin peptides. In view of these findings, the effect of angiotensin peptides on recovery after chemotherapy was assessed. Materials and methods: The effect of angiotensin 11 (All) and angiotensin(1-7) (A1-7) on the recovery of WBC and platelets in the blood, as well as the number of myeloid, erythroid and megakaryocyte progenitors in the bone marrow and the number of myeloid progenitors in the blood after intravenous administration of chemotherapeutic drugs was assessed in a mouse model. Results: In initial studies, subcutaneous administration of 10 or 100 mug/kg per day of All starting either 2 days before or 2 days after intravenous administration of 5-fluorouracil (5FU) accelerated WBC recovery (return to baseline between 7 and 14 days). Further, consistent with previous observations, the number of myeloid progenitors in the bone marrow and blood was increased after systemic administration of angiotensin peptides. The comparability of A(1-7) and All in their effect on hematopoietic recovery after chemotherapy was shown in subsequent studies. Daily administration of both AII and A(1-7) increased platelet numbers in the peripheral blood and myeloid, erythroid and megakaryocyte progenitors in the bone marrow. As 5FU is not a stem cell toxin, these studies were repeated with administration of A(1-7) initiated before or after intravenous cyclophosphamide. Following treatment with A(1-7) before cyclophosphamide the numbers of circulating WBC initially increased and then decreased starting on day 14. Following treatment with A(1-7) 2 days after cyclophosphamide the numbers of WBC and the numbers of myeloid progenitors increased in the peripheral blood and bone marrow. Conclusions: These findings suggest that angiotensin peptides accelerate hematopoietic recovery in multiple cellular lineages after chemotherapy, perhaps through an increase in the number of early hematopoietic progenitors.