Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses osteopetrosis in op/op mice.
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.
Lagasse
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Department of Pathology, Stanford University School of Medicine, California 94305, USA.
Weissman
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D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007728:Kupffer Cells / Q000166:cytology; D007958:Leukocyte Count; D008099:Liver / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D010022:Osteopetrosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000166:cytology
D019253:Proto-Oncogene Proteins c-bcl-2