Regulation of hematopoiesis by co-developing dendritic cells from human CD34+ cells.

通过人类 CD34 细胞共同发育树突状细胞来调节造血功能。

• 批准号: 14570959
• 负责人: SAWADA Kenichi
• 金额: $ 2.24万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570959/
• 关键词: CD34; Glycophorin A(GPA); Dendritic cells(DC); CD11c; Endocytosis; Phagocytosis; TNF-α; Human; GPA

Tumor necrosis factor-a (TNF-α) inhibits erythropoiesis and enhances non-erythroid colony formation. The present study examines the nature of these non-erythroid cells and investigates their physiological role in relation to erythroid progenitor cells. Highly purified human CD34^+ cells underwent erythroid differentiation in the presence of multiple cytokines, including stem cell factor (SCF), interleukin-3 (IL-3) and erythropoietin (EPO) with and without TNF-α. We enumerated colony-forming unit-erythroid (CFU-E) and glycophorin A (GPA ; a specific marker for erythroid lineage) positive cells in semisolid phase as well as in liquid suspension culture. The character and roles of co-developing non-erythroid cells in the presence of TNF-α were also analyzed using fluorescent activating cell sorter, enzyme immunohistochemistry and confocal microscopy. TNF-α inhibited the generation of GPA^+ cells and conversely enhanced the generation of GPA cells. The GPA cells were comprised of cells wit … More h excentric cell shape and were positive for HLA class I, HLA class II, CD1a, CD4, CD11c, CD14, CD40, CD80, CD83 and CD86, but not CD3, CD8, CD19, CD20 and CD56, indicating the co-development of dendritic cells (DC) along with erythroid differentiation. Developing DC/DC precursors were detected within 3 days of culture. Only in the presence of TNF-α, CD34^+ cells proliferated by forming aggregates where both GPA^+ and CD11c+ DC/DC precursors were present. During culture period, immature CD11c^+ DC were capable of endocytosing damaged GPA^+ cells. In conclusion, GPA cells co-generated from human CD34^+ cells during erythroid differentiation express DC phenotypes. CD11c^+ DC subset physically and selectively associates with developing immature erythorid cells and damaged self-GPA^+ cells and then obtains and captures self-substances. TNF-α is one of the earliest mediators of the acute phase response of inflammation and/or tissue damage. Therefore, our findings suggest that any acute phase response can facilitate rapid DC development from CD34^+ cells in bone marrow. Less

肿瘤坏死因子-α（TNF-α）抑制红细胞生成并增强非红系集落形成。本研究探讨了这些非红系细胞的性质，并调查他们的生理作用，红系祖细胞。高纯度的人CD 34 ^+细胞在多种细胞因子存在下经历红系分化，包括干细胞因子（SCF）、白细胞介素-3（IL-3）和促红细胞生成素（EPO），有或没有TNF-α。我们在半固体相以及液体悬浮培养物中计数了红系集落形成单位（CFU-E）和血型糖蛋白A（GPA ;红系谱系的特异性标志物）阳性细胞。采用荧光活化细胞分选仪、酶免疫组化和共聚焦显微镜分析TNF-α存在下共发育的非红系细胞的特征和作用。TNF-α抑制GPA^+细胞的生成，相反促进GPA细胞的生成。GPA细胞由具有以下结构的细胞组成： ...更多信息 HLA-I、HLA-II、CD 1a、CD 4、CD 11 c、CD 14、CD 40、CD 80、CD 83和CD 86均呈阳性，而CD 3、CD 8、CD 19、CD 20和CD 56均呈阴性，表明树突状细胞（DC）沿着红系分化。在培养的3天内检测到发育中的DC/DC前体。只有在TNF-α存在的情况下，CD 34 ^+细胞才通过在GPA^+和CD 11 c + DC/DC前体同时存在的地方形成聚集体而增殖。在培养过程中，未成熟的CD 11 c ^+ DC能够内吞受损的GPA^+细胞。总之，在红系分化过程中由人CD 34 ^+细胞共生成的GPA细胞表达DC表型。CD 11 c ^+ DC亚群选择性地与发育中的未成熟红细胞和受损的自身GPA ^+细胞发生物理性结合，获得并捕获自身物质。TNF-α是炎症和/或组织损伤的急性期反应的最早介质之一。因此，我们的研究结果表明，任何急性期反应都可以促进骨髓中CD 34 ^+细胞快速分化为DC。少

项目成果

Koizumi K.: "Severe aplastic anemia associated with thymic carcinoma and partial recovery of hematopoiesis after thymectomy."Ann Hematol. 82. 367-370 (2003)

Koizumi K.：“与胸腺癌相关的严重再生障碍性贫血和胸腺切除后造血功能部分恢复。”Ann Hematol。

Wakamoto S.: "Biologic activity of RANTES in apheresis PLT Concentrates and its involvement in nonhemolytic transfusion reactions."Transfusion. 43. 1038-1046 (2003)

Wakamoto S.：“RANTES 在单采 PLT 浓缩物中的生物活性及其在非溶血性输血反应中的作用。”输血。

Maki N.: "Four novel mutation in the Thiazide-Sensitive Na-Cl cotransporter in Japanese patients with gitelman's sybdrome."Nephrol Dial Transplant. (in press).

Maki N.：“日本 gitelman 综合征患者的噻嗪类敏感性 Na-Cl 协同转运蛋白中存在四种新突变。”肾拨号移植。

小泉和樹, 澤田賢一: "内科領域の輸血,輸血ハンドブック"台2版 霜山龍志 編集, 医学書院. 19 (2002)

小泉和树、泽田宪一：《内科输血、输血手册》，第 2 版，下山龙二编，医学书院 19（2002）。

Yamagushi M, Hirokawa F, Murahashi H, Azuma H, Miyazaki H, Fukazawa K, Sawada K, Koike T, Kuwabara M, Ikeda H, Ikebuchi K.: "Ex vivo expansion of human UC blood primitive hematopoletic progenitors and transplantable stern cells using human primary BM stro

Yamagushi M、Hirokawa F、Murahashi H、Azuma H、Miyazaki H、Fukazawa K、Sawada K、Koike T、Kuwabara M、Ikeda H、Ikebuchi K.：“使用体外扩增人 UC 血液原始造血祖细胞和可移植干细胞