Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses osteopetrosis in op/op mice
Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses osteopetrosis in op/op mice
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DOI：
10.1016/s0092-8674(00)80290-1
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发表时间：
1997-06-27
期刊：
影响因子：
64.5
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Lagasse, E;Weissman, IL
骨硬化（OP/OP）小鼠缺乏功能性M-CSF，并且巨噬细胞和破骨细胞水平降低。我们制备了在单核细胞中表达人Bcl-2的转基因小鼠（hMRP 8bcl-2）。体外hMRP 8bcl-2单核细胞在没有血清和M-CSF的情况下不发生凋亡，而op/op和野生型单核细胞死亡。这些表达Bcl-2的单核细胞自发地经历巨噬细胞分化。在体内，op/op hMRP 8bcl-2小鼠显示组织巨噬细胞的显著补充。他们的长骨骨硬化症在很大程度上得到逆转，骨髓中出现广泛的骨髓造血。我们认为，M-CSF增强单核细胞的生存，使他们能够响应内部和外部的线索，他们的分化。
Osteopetrotic (op/op) mice lack functional M-CSF and have depressed levels of macrophages and osteoclasts. We prepared transgenic mice (hMRP8bcl-2) that express human Bcl-2 in monocytes. in vitro hMRP8bcl-2 monocytes do not undergo apoptosis in the absence of serum and M-CSF, while op/op and wild-type monocytes die. These Bcl-2-expressing monocytes spontaneously undergo macrophage differentiation. In vivo, the op/op hMRP8bcl-2 mice show significant replenishment of tissue macrophages. Their long bone osteopetrosis is largely reversed, and extensive medullary hematopoiesis appears in the bone marrow. We propose that M-CSF augments monocyte survival, permitting them to respond to internal and external cues for their differentiation.