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干细胞因子单独及与粒细胞集落刺激因子(G-CSF)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)联合应用对啮齿动物体内外血液学的影响。

Hematologic effects of stem cell factor alone and in combination with G-CSF and GM-CSF in vivo and in vitro in rodents.

作者信息

Ulich T R, Yi E S, Yin S, del Castillo J, McNiece I, Yung Y P, Zsebo K M

机构信息

Department of Pathology, University of California San Diego Medical Center 92103.

出版信息

Int Rev Exp Pathol. 1993;34 Pt A:215-33.

PMID:7681048
Abstract

The intravenous injection of rrSCF causes neutrophilia and lymphocytosis as well as the appearance of immature myeloid cells and occasional blast cells in the circulation. The marrow shows a left-shifted myeloid and erythroid hyperplasia as evidenced by increases in numbers of morphologically recognizable early myeloid and erythroid precursors. A decrease in the number of mature marrow neutrophils is noted, suggesting that the release of marrow neutrophils contributes to the peripheral neutrophilia. After 2 weeks of daily injections of rrSCF, the marrow demonstrates a remarkable mast cell hyperplasia accompanied by erythroid and lymphoid hypoplasia. rrSCF causes mast cells to appear in the circulation and causes a systemic increase in embryonic connective tissue-type mast cells. In vitro long-term culture of mouse marrow cells with rrSCF results in an outgrowth of mast cells. The coinjection of rrSCF and G-CSF for 1 week causes a synergistic increase in mature marrow neutrophils accompanied by a striking decrease in erythroid and lymphoid marrow elements. Spleens demonstrate increased granulopoiesis as well as erythropoiesis as compared to the spleens of rats treated with single growth factors. Splenic extramedullary erythropoiesis may act to compensate for the decrease in marrow erythropoiesis. The coinjection of rrSCF and G-CSF causes an increase in marrow mast cells at the end of 1 week, but the increase is much less than in rats treated with rrSCF alone. The combination of rrSCF and G-CSF causes a synergistic peripheral neutrophilia. In vivo daily administration of SCF plus GM-CSF results in a synergistic increase in marrow neutrophils, but not the striking synergistic increase in circulating neutrophils that is observed after SCF plus G-CSF. Colony-forming assays reveal a synergistic increase in CFU-GMs in the marrow, but not in peripheral blood, after coincubation with SCF plus GM-CSF as opposed to GM-CSF alone, demonstrating anatomic compartmentalization between a more primitive marrow CFU-GM subset and a more mature peripheral blood CFU-GM subset.

摘要

静脉注射重组人干细胞因子(rrSCF)可导致中性粒细胞增多和淋巴细胞增多,以及循环中出现未成熟髓样细胞和偶见的原始细胞。骨髓显示髓系和红系增生左移,形态学上可识别的早期髓系和红系前体细胞数量增加证明了这一点。成熟骨髓中性粒细胞数量减少,提示骨髓中性粒细胞的释放导致外周血中性粒细胞增多。每日注射rrSCF 2周后,骨髓显示出显著的肥大细胞增生,伴有红系和淋巴系发育不全。rrSCF使肥大细胞出现在循环中,并导致胚胎结缔组织型肥大细胞全身性增加。用rrSCF对小鼠骨髓细胞进行体外长期培养会导致肥大细胞生长。rrSCF和粒细胞集落刺激因子(G-CSF)共同注射1周会导致成熟骨髓中性粒细胞协同增加,同时红系和淋巴系骨髓成分显著减少。与用单一生长因子处理的大鼠脾脏相比,脾脏显示粒细胞生成和红细胞生成增加。脾脏髓外红细胞生成可能起到补偿骨髓红细胞生成减少的作用。rrSCF和G-CSF共同注射在1周结束时会导致骨髓肥大细胞增加,但增加幅度远小于单独用rrSCF处理的大鼠。rrSCF和G-CSF的组合导致外周血中性粒细胞协同增多。在体内每日给予干细胞因子(SCF)加粒细胞巨噬细胞集落刺激因子(GM-CSF)会导致骨髓中性粒细胞协同增加,但不会像SCF加G-CSF后观察到的那样使循环中性粒细胞显著协同增加。集落形成试验显示,与单独使用GM-CSF相比,SCF加GM-CSF共同孵育后,骨髓中粒-巨噬细胞集落形成单位(CFU-GMs)协同增加,但外周血中没有,这表明更原始的骨髓CFU-GM亚群和更成熟的外周血CFU-GM亚群之间存在解剖学上的分隔。

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