In vivo administration of flt3 ligand markedly stimulates generation of dendritic cell progenitors from mouse liver.
In vivo administration of flt3 ligand markedly stimulates generation of dendritic cell progenitors from mouse liver.
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DOI：
10.4049/jimmunol.159.9.4268
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发表时间：
1997-11
影响因子：
4.4
通讯作者：
Maureen L. Drakes;Lina Lu;V. Subbotin;A. Thomson
中科院分区：
文献类型：
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作者：
Maureen L. Drakes;Lina Lu;V. Subbotin;A. Thomson
对肝树突状细胞 (DC) 及其祖细胞的研究受到从正常肝组织中分离或增殖的少量细胞的限制。在给小鼠注射最近克隆的造血生长因子 flt3 配体 (FL) 后，我们检查了这些细胞的离体生长、表型和功能，该配体在动员干细胞/祖细胞方面非常有效。与对照值相比，FL 治疗（10 微克/天，持续 10 天）导致从胶原酶消化的肝脏中回收的非实质细胞的绝对数量平均增加 14 倍。在粒细胞-巨噬细胞 CSF（GM-CSF；1000 U/ml）中培养这些非实质细胞，导致增殖细胞簇的早期形成和每个肝脏中非贴壁、低浮力密度细胞数量显着增加的最大释放（4-5 天内）。从对照肝脏繁殖的低浮力密度细胞的最大释放发生在6至8天的较晚时间。两个来源的细胞均为 DEC-205+、CD11c+、MHC II+ 类、CD80（低）（即低水平的 CD80）、CD86（低）和 CD40（低）。这种不成熟的表型与 T 细胞同种刺激活性较差有关，表明 DC 祖细胞。 FL处理小鼠肝脏细胞在GM-CSF和IL-4中的增殖导致更成熟的DC表型和功能。将 GM-CSF 刺激的祖细胞暴露于 1 型胶原蛋白额外 3 天后，还观察到成熟变化。 FL 促进大量肝脏 DC 祖细胞产生的能力为进一步研究正常肝脏免疫生物学和免疫介导的肝脏疾病中这些重要的 APC 提供了机会。
The study of liver dendritic cells (DC) and their progenitors is restricted by the small numbers that can be isolated or propagated from normal hepatic tissue. We examined the ex vivo growth, phenotype, and function of these cells after the administration to mice of the recently cloned hemopoietic growth factor flt3 ligand (FL), which is highly effective in mobilizing stem/progenitor cells. FL treatment (10 microg/day for 10 days) resulted in a mean 14-fold increase in the absolute number of nonparenchymal cells recovered from collagenase-digested livers compared with the control value. Culture of these nonparenchymal cells in granulocyte-macrophage CSF (GM-CSF; 1000 U/ml) resulted in the early formation of proliferating cell clusters and maximal release (within 4-5 days) of markedly increased numbers of nonadherent, low buoyant density cells per liver. Maximal release of low buoyant density cells propagated from control livers was at the later time of 6 to 8 days. Cells from both sources were DEC-205+, CD11c+, MHC class II+, CD80(low) (i.e., low level of CD80), CD86(low) and CD40(low). This immature phenotype was linked to poor T cell allostimulatory activity, indicative of DC progenitors. Propagation of cells from livers of FL-treated mice in GM-CSF and IL-4 resulted in a more mature DC phenotype and function. Maturational changes were also observed following exposure of the GM-CSF-stimulated progenitors to type 1 collagen for 3 additional days. The ability of FL to boost production of large numbers of liver DC progenitors provides opportunities for the further study of these important APC in normal liver immunobiology and in immune-mediated hepatic disorders.