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-a (TNF-α) 抑制红细胞生成并增强非红细胞集落形成。本研究检查了这些非红细胞集落的性质，并研究了它们与高度纯化的人 CD34^+ 相关的生理作用。细胞在多种细胞因子存在下进行红系分化，包括干细胞因子（SCF）、白细胞介素-3（IL-3）和促红细胞生成素我们计数了半固相和液体悬浮培养物中的集落形成单位红细胞 (CFU-E) 和血型糖蛋白 A（GPA；红细胞谱系的特异性标记）阳性细胞。还使用荧光激活细胞分选仪、酶免疫组织化学和共聚焦显微镜分析了 TNF-α 存在下共同发育的非红系细胞的特征和作用。 TNF-α 抑制 GPA^+ 细胞的生成，并相反增强 GPA 细胞的生成。GPA 细胞由具有偏心细胞形状的细胞组成，并且 HLA I 类、HLA II 类、CD1a、CD4、 CD11c、CD14、CD40、CD80、CD83 和 CD86，但不包括 CD3、CD8、CD19、CD20 和 CD56，表明树突共同发育仅在 TNF-α 存在的情况下，CD34^+ 细胞才会通过形成聚集体而增殖，其中 GPA^+ 和 CD11c+ DC/DC 前体细胞均在培养后 3 天内发生分化。在培养期间，未成熟的 CD11c^+ DC 能够内吞受损的 GPA^+ 细胞。 总之，GPA 细胞是由人 CD34^+ 共同生成的。红系分化过程中的细胞表达 CD11c^+ DC 子集，并选择性地与发育中的未成熟红系细胞和受损的自身 GPA^+ 细胞结合，然后获得并捕获自身物质 TNF-α 是最早的介质之一。炎症和/或组织损伤的急性期反应因此，我们的研究结果表明任何急性期反应都可以促进骨髓中 CD34^+ 细胞的快速 DC 发育。

项目成果

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）。

Maki N, Komatsuda A, Wakui H, Oyama Y, Kodama T, Ohtani A, Kigawa A, Imai H, Imai H, Motegi M, Yamaguchi A, Sawada K.: "A nonsense mutation (R220X) in the α-galactosidese A gene causes typical Fabry disease in both genders."Clinical Nephrol. (in press).

Maki N、Komatsuda A、Wakui H、Oyama Y、Kodama T、Ohtani A、Kikawa A、Imai H、Imai H、Motegi M、Yamaguchi A、Sawada K.：“α-半乳糖苷 A 中的无义突变 (R220X)基因会导致两性的典型法布里病。”《临床肾病》（Clinical Nephrol）。（出版中）。

Fukaya H, Xiao W, Inaba K, Suzuki Y, Hirokawa M, Kawabata Y, Komatsuda A, Endo T, Kishimoto H, Takada G, Sawada K.: "Co-development of dendritic cells along with erythroid differentiation from human CD34 ; cells by tumor necrosis factor-α."Exp Hematol. (i

Fukaya H、Xiao W、Inaba K、Suzuki Y、Hirokawa M、Kawabata Y、Komatsuda A、Endo T、Kishimoto H、Takada G、Sawada K.：“树突状细胞与人类 CD34 细胞的红系分化的共同发育；通过肿瘤坏死因子-α。“Exp Hematol。（i

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。