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白血病红细胞祖细胞与骨髓巨噬细胞之间的关联。

Association between leukemic erythroid progenitors and bone marrow macrophages.

作者信息

Breton-Gorius J, Vuillet-Gaugler M H, Coulombel L, Guichard J, Teillet F, Vainchenker W

机构信息

INSERM U.91 Hôpital Henri Mondor, Créteil, France.

出版信息

Blood Cells. 1991;17(1):127-42; discussion 142-6.

PMID:2018849
Abstract

Previous ultrastructural investigations have shown that the erythroblastic island is composed of erythroblasts at different stages of maturation which are intimately associated with a central macrophage. However, it is still unclear at which stage of erythroid differentiation this interaction occurs, mainly because of the lack of purified populations of normal erythroid progenitors [erythroid colony-forming units (CFU-E) and erythroid burst-forming units (BFU-E)] and early precursor cells (proerythroblasts) and because of our limited knowledge of their ultrastructural characteristics. In the present work we analyzed the ultrastructure of CFU-E enriched from normal human bone marrow by avidin-biotin immune rosetting and leukemic blasts of erythroid origin from two patients. Normal and leukemic CFU-Es were defined as glycophorin A (GPA)-negative blasts, devoid of rhopheocytosis, containing some ferritin molecules, either free in the cytoplasm or associated with theta-granules (theta-Gr) in the Golgi zone. Peroxidase activity was detected in the endoplasmic reticulum of these blasts. A preproerythroblast stage was identified, which corresponded to an intermediate phenotype with few GPA sites and rhopheocytosis. In contrast to hemoglobin synthesis, which was absolutely dependent on the presence of erythropoietin (Epo) during culture for 24 hours, ferritin molecules accumulated in the absence of Epo. Interestingly, leukemic CFU-E-like blasts were always in contact with bone marrow macrophages and adhesion between these cell types resisted mechanical dissociation. This result suggests that erythroid progenitors may be part of the erythroblastic island. The mechanisms involved in erythroblast-macrophage binding are still unknown, but the expression by macrophages and erythroid progenitors of receptors for fibronectin and thrombospondin (TSP), as well as their respective ligands in the case of macrophages, suggests that these molecules could be involved in the formation of the erythroblastic island.

摘要

以往的超微结构研究表明,成红细胞岛由处于不同成熟阶段的成红细胞组成,这些成红细胞与中央巨噬细胞紧密相连。然而,这种相互作用发生在红系分化的哪个阶段仍不清楚,主要原因是缺乏正常红系祖细胞(红系集落形成单位[CFU-E]和红系爆式集落形成单位[BFU-E])以及早期前体细胞(早幼红细胞)的纯化群体,并且我们对它们的超微结构特征了解有限。在本研究中,我们分析了通过抗生物素蛋白-生物素免疫玫瑰花结法从正常人骨髓中富集的CFU-E以及两名患者的红系来源白血病原始细胞的超微结构。正常和白血病CFU-E被定义为血型糖蛋白A(GPA)阴性的原始细胞,无吞噬红细胞现象,含有一些铁蛋白分子,这些分子要么游离于细胞质中,要么与高尔基体区域的θ颗粒(θ-Gr)相关联。在这些原始细胞的内质网中检测到过氧化物酶活性。确定了一个早幼红细胞前体阶段,其对应于具有少量GPA位点和吞噬红细胞现象的中间表型。与血红蛋白合成不同,血红蛋白合成在培养24小时期间绝对依赖于促红细胞生成素(Epo)的存在,而铁蛋白分子在没有Epo的情况下会积累。有趣的是,白血病CFU-E样原始细胞总是与骨髓巨噬细胞接触,并且这些细胞类型之间的黏附抵抗机械解离。这一结果表明红系祖细胞可能是成红细胞岛的一部分。成红细胞与巨噬细胞结合所涉及的机制仍然未知,但巨噬细胞和红系祖细胞对纤连蛋白和血小板反应蛋白(TSP)受体的表达,以及巨噬细胞情况下它们各自的配体,表明这些分子可能参与成红细胞岛的形成。

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