Angiotensin-(1-7) synergizes with colony-stimulating factors in hematopoietic recovery.
Angiotensin-(1-7) synergizes with colony-stimulating factors in hematopoietic recovery.
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血管紧张素-(1-7) 在造血恢复中与集落刺激因子协同作用。
DOI：
10.1007/s00280-013-2312-9
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发表时间：
2013
影响因子：
3
通讯作者：
diZerega,GereS
中科院分区：
文献类型：
--
作者：
Rodgers,KathleenE;Espinoza,TheresaB;Roda,Norma;Meeks,ChristopherJ;diZerega,GereS
目的血管紧张素（1-7）[A（1-7）]是肾素血管紧张素系统的一种活性肽，具有刺激骨髓祖细胞数量和骨髓抑制后造血恢复的作用。我们评估了A（1-7）与集落刺激因子，Neupogen和Epogen的组合，对骨髓祖细胞和化疗后循环形成元素的恢复。随着时间的推移，循环血细胞和骨髓祖细胞进行了测量。结果A（1-7）与Neupogen（后者仅给予3天开始在白色血细胞最低点）的组合减少了Neupogen的量需要最佳的恢复10倍。测定的祖细胞包括CFU-GEMM、CFU-GM、CFU-Meg和BFU-E。A（1-7）在单独给予或与Neupogen联合给予时，使所有祖细胞的恢复率高于单独给予Neupogen。A（1-7）与Epogen的组合略微增加（不显著）红细胞浓度，高于单独使用Epogen所达到的浓度。然而，在该模型中，A（1-7）或A（1-7）与Epogen组合增加了所有红系祖细胞，对早期红系祖细胞的作用最大结论Neupogen和Epogen与A（1-7）有协同作用，化疗后骨髓中的巨核细胞和红系祖细胞表明A（1-7）对骨髓中早期祖细胞的多谱系效应促进了响应谱系特异性生长因子的增殖。
PurposeAngiotensin (1–7) [A(1–7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1–7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and the recovery of circulating formed elements following chemotherapy.MethodsMice were injected with gemcitabine followed 2 days later with A(1–7). Circulating blood cells and bone marrow progenitors were measured over time.ResultsCombination of A(1–7) with Neupogen (the latter given only 3 days starting at the white blood cell nadir) decreased the amount of Neupogen needed for optimal recovery by 10-fold. The progenitors measured include CFU-GEMM, CFU-GM, CFU-Meg and BFU-E. A(1–7) increased recovery of all progenitors when given alone or in combination with Neupogen above that with Neupogen alone. Combination of A(1–7) with Epogen slightly increased (not significantly) red blood cell concentrations above those achieved by Epogen alone. However, in this model, A(1–7) or A(1–7) in combination with Epogen increased all erythroid progenitors with the largest effect on early erythroid progenitors (immature BFU-E).ConclusionsNeupogen and Epogen acted synergistically with A(1–7) to increase the concentration of myeloid, megakaryocytic and erythroid progenitor cells in the bone marrow following chemotherapy suggesting that A(1–7)’s multilineage effect on early progenitors in the marrow facilitates proliferation in response to lineage-specific growth factors.