TNF-related apoptosis-inducing ligand (TRAIL) as a negative regulator of normal human erythropoiesis

作     者：Zamai, L Secchiero, P Pierpaoli, S Bassini, A Papa, S Alnemri, ES Guidotii, L Vitale, M Zauli, G 

作者机构：Univ Urbino Inst Morphol Sci I-61029 Urbino Italy Univ Ferrara Dept Morphol & Embryol Human Anat Sect I-44100 Ferrara Italy Univ Bologna Inst Histol & Gen Embryol Bologna Italy Thomas Jefferson Univ Jefferson Med Coll Kimmel Canc Inst Philadelphia PA 19107 USA Univ Brescia Dept Biomed Sci & Biotechnol Human Anat Sect Brescia Italy CNR NP Inst Cytomorphol Codivilla Putti Res Inst I-40126 Bologna Italy Univ Chieti Inst Human Morphol G DAnnunzio Chieti Italy 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第12期

页      面：3716-3724页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NCI NIH HHS [CA78890] Funding Source: Medline 

主　　题：抗原 CD/分析 抗原 CD15/分析 抗原 CD34/分析 细胞凋亡/药物作用 凋亡调节蛋白质类 骨髓细胞/细胞学 细胞存活/药物作用 细胞 培养的 集落形成单位测定 红细胞生成/药物作用 红细胞生成/生理学 流式细胞术 造血干细胞/细胞学 造血干细胞/药物作用 造血干细胞/生理学 配体 膜糖蛋白类/药理学 重组蛋白质类/药理学 TNF相关凋亡诱导配体 肿瘤坏死因子α/药理学 成年人 人类 

摘      要：The impact of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal hematopoietic development was investigated using adult peripheral blood CD34(+) hematopoietic progenitor cells, induced to differentiate along the erythroid, megakaryocytic, granulocytic, and monocytic lineages by the addition of specific cytokine cocktails. TRAIL selectively reduced the number of erythroblasts, showing intermediate levels of glycophorin A (glycophorin A(interm)) surface expression, which appeared in liquid cultures supplemented with stem cell factor + interleukin 3 + erythropoietin at days 7-10. However, neither immature (day 4) glycophorin A(dim) erythroid cells nor mature (day 14) glycophorin A(bright) erythroblasts were sensitive to TRAIL-mediated apoptosis, Moreover, preexposure to TRAIL significantly decreased the number and size of erythroid colonies in semisolid assays, These adverse effects of TRAIL were selective for erythropoiesis, as TRAIL did not significantly influence the survival of cells differentiating along the megakaryocytic, granulocytic, or monocytic lineages, Furthermore, TRAIL was detected by Western blot analysis in lysates obtained from normal bone marrow mononuclear cells, These findings indicate that TRAIL acts in a lineage- and stage of differentiation-specific manner, as a negative regulator of normal erythropoiesis. (C) 2000 by The American Society of Hematology.