Hematopoietic properties of granulocyte colony-stimulating factor/immunoglobulin (G-CSF/IgG-Fc) fusion proteins in normal and neutropenic rodents.
Hematopoietic properties of granulocyte colony-stimulating factor/immunoglobulin (G-CSF/IgG-Fc) fusion proteins in normal and neutropenic rodents.
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DOI：
10.1371/journal.pone.0091990
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Doherty DH
中科院分区：
文献类型：
--
作者：
Cox GN;Chlipala EA;Smith DJ;Carlson SJ;Bell SJ;Doherty DH
此前我们表明，当粒细胞集落刺激因子（G-CSF）通过灵活的7个氨基酸接头连接至免疫球蛋白-1（IgG1）-Fc结构域时，该蛋白的体外生物活性得以保留，并且与正常大鼠中的G-CSF相比，G-CSF/IgG1-Fc融合蛋白具有更长的循环半衰期和改善的造血特性。我们通过比较正常小鼠中 G-CSF/IgG1-Fc 与 G-CSF 以及中性粒细胞减少大鼠中 G-CSF 和聚乙二醇 (PEG) 修饰的 G-CSF 的相对造血效力，扩展了该分析。使用不同剂量和给药方案的 G-CSF/IgG1-Fc 或 G-CSF 治疗小鼠 5 天，并在第 6 天测量动物的循环中性粒细胞水平。当使用每天、每隔一天或每三天的给药方案施用时，与相当剂量的 G-CSF 相比，G-CSF/IgG1-Fc 刺激血液中性粒细胞更大的增加。在用环磷酰胺造成中性粒细胞减少的大鼠中，每天注射 5 次或第 1 天单次注射时，G-CSF/IgG1-Fc 加速血液中性粒细胞恢复至正常水平（从第 9 天到第 5 天）。相比之下，每天注射 5 次时，G-CSF 加速中性粒细胞恢复，但单次注射时则不然。在中性粒细胞减少大鼠中单次注射后，G-CSF/IgG1-Fc 在加速中性粒细胞恢复方面与 PEG-G-CSF 一样有效。删除了 7 个氨基酸接头的 G-CSF/IgG1-Fc 和 G-CSF/IgG4-Fc 融合蛋白在中性粒细胞减少大鼠中单次注射后也能有效加速中性粒细胞恢复。这些研究证实了 G-CSF/IgG-Fc 融合蛋白增强的体内造血特性。
Previously we showed that granulocyte colony-stimulating factor (G-CSF) in vitro bioactivity is preserved when the protein is joined via a flexible 7 amino acid linker to an immunoglobulin-1 (IgG1)-Fc domain and that the G-CSF/IgG1-Fc fusion protein possessed a longer circulating half-life and improved hematopoietic properties compared to G-CSF in normal rats. We have extended this analysis by comparing the relative hematopoietic potencies of G-CSF/IgG1-Fc to G-CSF in normal mice and to G-CSF and polyethylene glycol (PEG) - modified G-CSF in neutropenic rats. Mice were treated for 5 days using different doses and dosing regimens of G-CSF/IgG1-Fc or G-CSF and circulating neutrophil levels in the animals measured on Day 6. G-CSF/IgG1-Fc stimulated greater increases in blood neutrophils than comparable doses of G-CSF when administered using daily, every other day or every third day dosing regimens. In rats made neutropenic with cyclophosphamide, G-CSF/IgG1-Fc accelerated recovery of blood neutrophils to normal levels (from Day 9 to Day 5) when administered as 5 daily injections or as a single injection on Day 1. By contrast, G-CSF accelerated neutrophil recovery when administered as 5 daily injections, but not when administered as a single injection. G-CSF/IgG1-Fc was as effective as PEG-G-CSF at accelerating neutrophil recovery following a single injection in neutropenic rats. G-CSF/IgG1-Fc and G-CSF/IgG4-Fc fusion proteins in which the 7 amino acid linker was deleted also were effective at accelerating neutrophil recovery following a single injection in neutropenic rats. These studies confirm the enhanced in vivo hematopoietic properties of G-CSF/IgG-Fc fusion proteins.
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影响因子：
11.4
作者：
DANGL, JL;WENSEL, TG;OI, VT
通讯作者：
OI, VT
影响因子：
2.6
作者：
Cox, GN;Smith, DJ;Doherty, DH
通讯作者：
Doherty, DH
DOI：
10.1385/0-89603-244-2:251
发表时间：
1993-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Horton, R M
通讯作者：
Horton, R M
影响因子：
3.6
作者：
Schuurman, J;Perdok, GJ;Aalberse, RC
通讯作者：
Aalberse, RC
影响因子：
2.6
作者：
Molineux, G;Kinstler, O;Schwab, G
通讯作者：
Schwab, G