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小鼠肥大细胞生长因子(c-kit原癌基因配体)对人骨髓造血祖细胞集落形成的影响。

Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells.

作者信息

Broxmeyer H E, Cooper S, Lu L, Hangoc G, Anderson D, Cosman D, Lyman S D, Williams D E

机构信息

Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202-5121.

出版信息

Blood. 1991 May 15;77(10):2142-9.

PMID:1709371
Abstract

Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte-macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhuIL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhuIL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34 HLA-DR+ and CD34 HLA-DR+CD33- sorted cells in which greater than or equal to 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.

摘要

对纯化的天然(n)和重组(r)小鼠(mu)肥大细胞生长因子(MGF,一种c-kit配体)进行了评估,其单独使用以及与重组人(hu)促红细胞生成素(Epo)、重组人粒细胞-巨噬细胞集落刺激因子(rhuGM-CSF)、重组人粒细胞集落刺激因子(rhuG-CSF)和/或重组人巨噬细胞集落刺激因子(rhuM-CSF)联合使用时,对正常人骨髓中的多能(集落形成单位-粒细胞、红细胞、单核细胞、巨核细胞[CFU-GEMM])、红细胞(爆式红细胞集落形成单位[BFU-E])和粒细胞-巨噬细胞(CFU-GM)祖细胞的体外集落形成的影响。MGF是Epo依赖性CFU-GEMM和BFU-E集落形成的强效增强细胞因子,与重组人白细胞介素-3(rhuIL-3)或rhuGM-CSF相比,它能刺激更多且更大的集落。MGF,尤其是在较低浓度下,还与rhuIL-3或rhuGM-CSF共同作用以增强Epo依赖性CFU-GEMM和BFU-E集落形成。MGF本身对CFU-GM集落的刺激活性很小,但与次优至最佳量的rhuGM-CSF联合使用时,以相加至大于相加的方式增加CFU-GM集落的数量和大小。虽然我们未检测到MGF对rhuG-CSF最大浓度刺激的CFU-G集落数量有影响,但MGF确实增加了CFU-G衍生集落的大小。MGF并未增强rhuM-CSF的活性。在一项比较试验中,rmu和rhuMGF的最大浓度在增强人骨髓集落形成方面同样有效,但与rmuMGF不同,rhuMGF在测试浓度下并未增强小鼠骨髓细胞的集落形成。MGF对BFU-E、CFU-GM和CFU-GEMM的作用可能是直接作用,因为在CD34 HLA-DR +和CD34 HLA-DR + CD33-分选细胞的高度富集祖细胞群体中,MGF增强了这些细胞的集落形成,其中2个细胞中大于或等于1个是BFU-E加CFU-GM加CFU-GEMM。MGF似乎是一种早期作用的细胞因子,优先刺激未成熟造血祖细胞的生长。

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