Myeloid development is selectively disrupted in PU.1 null mice
| Autor: | K L, Anderson, K A, Smith, K, Conners, S R, McKercher, R A, Maki, B E, Torbett |
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| Rok vydání: | 1998 |
| Předmět: |
Neutrophils
Drug Resistance Receptor Macrophage Colony-Stimulating Factor Monocytes Colony-Forming Units Assay Mice Proto-Oncogene Proteins Granulocyte Colony-Stimulating Factor Animals Cells Cultured Mice Knockout Macrophage Colony-Stimulating Factor Macrophages Immunologic Deficiency Syndromes Granulocyte-Macrophage Colony-Stimulating Factor Cell Differentiation Leukopenia Hematopoietic Stem Cells Lymphocyte Subsets Hematopoiesis Mice Inbred C57BL Phenotype Receptors Granulocyte-Macrophage Colony-Stimulating Factor Receptors Granulocyte Colony-Stimulating Factor Trans-Activators Cell Division |
| Zdroj: | Blood. 91(10) |
| ISSN: | 0006-4971 |
| Popis: | The ets family transcription factor PU.1 is expressed in monocytes/macrophages, neutrophils, mast cells, B cells, and early erythroblasts, but not in T cells. We have recently shown that PU.1 gene disruption results in mice with no detectable monocytes/macrophages and B cells but T-cell development is retained. Although neutrophil development occurred in these mice, it was delayed and markedly reduced. We now proceed to demonstrate that PU. 1 null hematopoietic cells fail to proliferate or form colonies in response to macrophage colony-stimulating factor (M-CSF), granulocyte CSF (G-CSF), and granulocyte/macrophage CSF (GM-CSF). In contrast, PU.1 null cells did proliferate and form colonies in response to interleukin-3 (IL-3), although the response was reduced as compared with control littermates. Compared with control cells, PU.1 null cells had minimal expression of G- and GM-CSF receptors and no detectable M-CSF receptors. The size of individual myeloid colonies produced from PU.1 null primitive and committed myeloid progenitors in the presence of IL-3, IL-6, and stem cell factor (SCF) were reduced compared with controls. Under these conditions, PU.1 null progenitors produced neutrophils but not monocytes/macrophages. These observations suggest that PU.1 gene disruption induces additional cell-autonomous effects that are independent of the alterations in myeloid growth factor receptor expression. Our results demonstrate that PU.1 gene disruption affects a number of developmentally regulated hematopoietic processes that can, at least in part, explain the changes in myeloid development and reduction in myeloid and neutrophil expansion observed in PU.1 null mice. |
| Databáze: | OpenAIRE |
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