Intravenous injection of naked DNA encoding secreted flt3 ligand dramatically increases the number of dendritic cells and natural killer cells in vivo
Intravenous injection of naked DNA encoding secreted flt3 ligand dramatically increases the number of dendritic cells and natural killer cells in vivo
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DOI：
10.1089/10430340050015734
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发表时间：
2000-03-01
影响因子：
4.2
通讯作者：
Huang, L
中科院分区：
文献类型：
--
作者：
He, YK;Pimenov, AA;Huang, L
组织中存在的树突状细胞（DCs）的痕量限制了DC生物学的研究和利用DC的临床应用的发展。在这里，我们显示编码分泌的人flt 3配体（hFLex）的裸DNA的基于流体动力学的基因递送可以显著增加功能性DCs和自然杀伤（NK）细胞的数量。在单次注射hFLex基因后，小鼠血清中的hFLex水平达到约40 μ g/ml，并在5-6天内保持在1 μ g/ml以上。持续的血清hFLex水平与淋巴器官的大小以及淋巴结和脾脏中树突状细胞和NK细胞的比例显著增加相关。DC和NK细胞数量从第5天开始增加，并在第8天至第12天达到高峰，然后在第20天恢复正常。这些DC和NK细胞的功能分别通过混合白细胞反应和YAC-1细胞裂解来证明。这些结果表明，hFLex基因的递送提供了一种简单、有效和廉价的增加体内DC和NK细胞群体的方法，并且在DC和NK细胞生物学的进一步研究和免疫治疗策略的开发中可能具有广泛的应用。
The trace number of dendritic cells (DCs) present in tissues has limited the study of DC biology and development of clinical applications utilizing DCs, Here we show that hydrodynamics-based gene delivery of naked DNA encoding secreted human flt3 ligand (hFLex) can dramatically increase the number of functional DCs and natural killer (NK) cells. After a single injection of the hFLex gene, hFLex levels in mouse serum reached approximately 40 mu g/ml and remained above 1 mu g/ml for 5-6 days. Sustained levels of serum hFLex correlated with significant increases in the size of the lymphoid organs and in the proportion of dendritic cells and NK cells in both lymph nodes and spleen. The increase in DC and NK cell numbers started from day 5, and reached peak levels between day 8 and day 12, The levels then returned to normal on day 20. These DCs and NK cells were functional as evidenced by mixed leukocyte reactions and lysis of YAC-1 cells, respectively, These results suggest that delivery of the hFLex gene provides a simple, efficient, and inexpensive way of increasing DC and NK cell populations in vivo, and may have broad applications in the further study of DC and NK cell biology and in the development of immunotherapy strategies.