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The promoter of macrophage colony-stimulating factor receptor is active in astrocytes
1PRPG, Hofmann-La Roche AG, Basel, Switzerland.
Abstract:
Macrophage colony-stimulating factor (M-CSF) is a hematopoietin whose actions are essential for growth and survival of macrophages, placental development, ramification of microglia and tumor progression. The expression of the receptor for macrophage colony-stimulating factor (c-fms) is regulated by two distinct promoters: distal and proximal. The distal promoter is active in trophoblasts during embryogenesis and the proximal promoter directs expression to the cells of myeloid lineage. Here we report the generation of transgenic mice expressing beta-galactosidase under the control of the human proximal c-fms promoter and demonstrate the promoter activity in astrocytes, cells of neurological origin that partially take over the role of the macrophages in the central nervous system. Enzymatic activity of beta-galactosidase was detected in homogenated spleen, bone marrow and brain and in the cell extracts from peritoneal macrophages of transgenic mice. Immunohistochemical staining of brain showed the presence of beta-galactosidase in astrocytes. We hypothesize that M-CSF released by astrocytes, upon stimulation by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or interleukin-1 (IL-1), regulates the expression of its own receptor.
Insights
Macrophage colony-stimulating factor (M-CSF) receptor expression in the brain was studied using transgenic mice. The proximal c-fms promoter is active in astrocytes, suggesting a role for M-CSF in neurological functions.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Macrophage colony-stimulating factor (M-CSF) is crucial for macrophage survival and function.
- M-CSF receptor (c-fms) expression is regulated by distinct promoters.
- The proximal c-fms promoter directs expression in myeloid cells.
Purpose of the Study:
- To investigate the activity of the proximal c-fms promoter in the central nervous system.
- To identify novel cell types expressing the M-CSF receptor.
- To explore the potential role of M-CSF in neurological processes.
Main Methods:
- Generation of transgenic mice with beta-galactosidase under the proximal c-fms promoter.
- Enzymatic assays for beta-galactosidase activity in spleen, bone marrow, and brain.
- Immunohistochemical staining of brain tissue to localize promoter activity.
Main Results:
- Beta-galactosidase activity was detected in spleen, bone marrow, and brain homogenates.
- Enzymatic activity was confirmed in peritoneal macrophages.
- Immunohistochemistry revealed beta-galactosidase expression specifically in astrocytes within the brain.
Conclusions:
- The proximal c-fms promoter is active in astrocytes, cells of neurological origin.
- This finding suggests a potential role for M-CSF signaling in the central nervous system.
- Astrocytes may contribute to M-CSF regulation of its own receptor in response to inflammatory stimuli.