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Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells
Frauke Forstreuter1, Ralph Lucius, Rolf Mentlein
1Department of Anatomy, University of Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany.
Abstract:
Vascular endothelial growth factor (VEGF) is an angiogenic peptide that is produced in the brain after ischemia, injury or in malignant gliomas. Since these pathological conditions are associated with the infiltration of microglial cells, we investigated the expression of VEGF receptors (VEGFR) and possible effects of VEGF on cultivated microglial cells. As shown by reverse transcription-polymerase chain reaction and immunocytochemistry, rat microglial cells as well as the murine cell line BV-2 express the VEGFR-1, but not VEGFR-2. Murine VEGF induced 3H-thymidine incorporation into DNA of murine and rat microglial cells as well as chemotaxis in Boyden chamber assays. However, VEGF did not alter the phosphorylation of mitogen-activated protein kinases and only slightly that of the kinase Akt. These results show that microglial cells are targets for VEGF which induces migration and proliferation of these immunocompetent cells in the brain.
Insights
Vascular endothelial growth factor (VEGF) targets brain microglial cells, promoting their migration and proliferation. This suggests a role for VEGF in brain injury and disease by influencing these immune cells.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Vascular endothelial growth factor (VEGF) is implicated in brain pathologies like ischemia, injury, and gliomas.
- Microglial cells infiltrate the brain during these pathological conditions.
Purpose of the Study:
- To investigate the expression of VEGF receptors (VEGFR) on microglial cells.
- To determine the effects of VEGF on microglial cell behavior.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect VEGFR gene expression.
- Immunocytochemistry to visualize VEGFR protein on cells.
- 3H-thymidine incorporation assays to measure DNA synthesis (proliferation).
- Boyden chamber assays to assess cell migration (chemotaxis).
Main Results:
- Rat and murine microglial cells (BV-2 cell line) express VEGFR-1 but not VEGFR-2.
- VEGF stimulated DNA synthesis and chemotaxis in both rat and murine microglial cells.
- VEGF had minimal impact on mitogen-activated protein kinase and Akt phosphorylation.
Conclusions:
- Microglial cells are identified as targets for VEGF.
- VEGF signaling in microglial cells promotes their migration and proliferation.
- VEGF may play a significant role in brain immune responses during pathological conditions.