McKenna H J, Stocking K L, Miller R E, Brasel K, De Smedt T, Maraskovsky E, Maliszewski C R, Lynch D H, Smith J, Pulendran B, Roux E R, Teepe M, Lyman S D, Peschon J J
Immunex Corporation, Seattle, WA 98101, USA.
Blood. 2000 Jun 1;95(11):3489-97.
The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (flt3), also referred to as fetal liver kinase-2 (flk-2), has an important role in hematopoiesis. The flt3 ligand (flt3L) is a growth factor for hematopoietic progenitors and induces hematopoietic progenitor and stem cell mobilization in vivo. In addition, when mice are treated with flt3L immature B cells, natural killer (NK) cells and dendritic cells (DC) are expanded in vivo. To further elucidate the role of flt3L in hematopoiesis, mice lacking flt3L (flt3L-/-) were generated by targeted gene disruption. Leukocyte cellularity was reduced in the bone marrow, peripheral blood, lymph nodes (LN), and spleen. Thymic cellularity, blood hematocrit, and platelet numbers were not affected. Significantly reduced numbers of myeloid and B-lymphoid progenitors were noted in the BM of flt3L-/- mice. In addition a marked deficiency of NK cells in the spleen was noted. DC numbers were also reduced in the spleen, LN, and thymus. Both myeloid-related (CD11c(++) CD8alpha(-)) and lymphoid-related (CD11c(++) CD8alpha(+)) DC numbers were affected. We conclude that flt3L has an important role in the expansion of early hematopoietic progenitors and in the generation of mature peripheral leukocytes.
受体酪氨酸激酶fms样酪氨酸激酶3（Flt3）的配体，也被称为胎儿肝激酶-2（Flk-2），在造血过程中发挥着重要作用。Flt3配体（Flt3L）是造血祖细胞的生长因子，可在体内诱导造血祖细胞和干细胞的动员。此外，当用Flt3L处理小鼠时，未成熟B细胞、自然杀伤（NK）细胞和树突状细胞（DC）在体内会增多。为了进一步阐明Flt3L在造血过程中的作用，通过靶向基因破坏产生了缺乏Flt3L（Flt3L-/-）的小鼠。骨髓、外周血、淋巴结（LN）和脾脏中的白细胞细胞数量减少。胸腺细胞数量、血细胞比容和血小板数量未受影响。在Flt3L-/-小鼠的骨髓中，髓系和B淋巴细胞祖细胞数量显著减少。此外，脾脏中NK细胞明显缺乏。脾脏、LN和胸腺中的DC数量也减少。髓系相关（CD11c（++）CD8α（-））和淋巴系相关（CD11c（++）CD8α（+））DC数量均受影响。我们得出结论，Flt3L在早期造血祖细胞的扩增以及成熟外周白细胞的生成中起重要作用。
