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Murine astrocytes express a functional chemokine receptor
S Tanabe1, M Heesen, M A Berman
1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Summary
Chemokines like macrophage inflammatory protein-1alpha (MIP-1alpha) attract astrocytes, a key finding for CNS inflammation. This astrocyte chemotaxis is mediated by the CCR1 receptor and involves Galphai proteins.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Chemokines are implicated in Central Nervous System (CNS) diseases.
- The impact of chemokines on CNS parenchymal cells remains largely unexplored.
Purpose of the Study:
- To investigate astrocyte chemotaxis towards macrophage inflammatory protein-1alpha (MIP-1alpha).
- To identify the specific chemokine receptors involved in astrocyte responses to MIP-1alpha.
Main Methods:
- Murine astrocytes were exposed to varying concentrations of MIP-1alpha.
- Chemotaxis was assessed, and responses were tested for inhibition by pertussis toxin.
- Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization were used to detect chemokine receptor mRNA expression.
Main Results:
- Murine astrocytes exhibited directed migration in response to MIP-1alpha (10^-10 to 10^-8 M), with peak response at 10^-9 M.
- MIP-1alpha-induced astrocyte migration was inhibited by pertussis toxin, indicating involvement of Galphai proteins.
- Astrocytes express mRNA for the MIP-1alpha receptor CCR1, but not CCR4 or MIP-1alphaR-like#1.
Conclusions:
- Astrocytes possess a functional chemokine receptor (CCR1) mediating directed migration.
- Chemokine-astrocyte interactions are likely involved in CNS inflammatory processes.