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Amyloid-beta-induced chemokine production in primary human macrophages and astrocytes
Hessel A Smits1, Annemarie Rijsmus, Joyce H van Loon
1Section Neuroimmunology, Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, University Medical Center Utrecht, Heidelberglaan 100, NL-3584 CX Utrecht, The Netherlands.
Abstract:
In Alzheimer's disease (AD), chemotaxis might be responsible for attracting glial cells towards the neuritic plaque. Using primary monocyte-derived macrophages and primary adult astrocytes as a model, amyloid-beta (Abeta) (1-42) was able to stimulate the production, as measured by RT-PCR, of MIP-1alpha and MIP-1beta mRNA in macrophages and MCP-1 in astrocytes. Cocultures showed in unstimulated as well as in Abeta-stimulated cells an increase in MIP-1alpha, MIP-1beta and MCP-1 mRNA. ELISAs of supernatant samples of stimulated macrophages and astrocytes also showed an increase in MIP-1alpha and MIP-1beta in macrophages and MCP-1 in astrocytes. Stimulated cocultures showed an increase in MIP-1alpha, MIP-1beta and MCP-1 protein levels in contrast to unstimulated cocultures.
Insights
Alzheimer's disease (AD) involves amyloid-beta (Abeta) stimulating glial cells. Macrophages and astrocytes produce inflammatory signals (MIP-1alpha, MIP-1beta, MCP-1) in response to Abeta, contributing to AD pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Chemotaxis of glial cells towards neuritic plaques is implicated in Alzheimer's disease (AD) pathogenesis.
- Amyloid-beta (Abeta) is a key component of neuritic plaques in AD.
Purpose of the Study:
- To investigate the role of amyloid-beta (Abeta) in stimulating glial cell chemokine production.
- To model the chemotactic response of macrophages and astrocytes to Abeta in Alzheimer's disease.
Main Methods:
- Primary monocyte-derived macrophages and adult astrocytes were used as cellular models.
- Cells were stimulated with amyloid-beta (Abeta) (1-42).
- Messenger RNA (mRNA) and protein levels of chemokines (MIP-1alpha, MIP-1beta, MCP-1) were measured using RT-PCR and ELISA.
Main Results:
- Amyloid-beta (Abeta) stimulated the production of MIP-1alpha and MIP-1beta mRNA in macrophages.
- Amyloid-beta (Abeta) stimulated the production of MCP-1 mRNA in astrocytes.
- Both mRNA and protein levels of these chemokines increased in stimulated macrophages, astrocytes, and cocultures.
Conclusions:
- Amyloid-beta (Abeta) directly stimulates macrophages and astrocytes to produce chemokines involved in glial cell recruitment.
- These findings support a role for Abeta-induced chemotaxis in the inflammatory response observed in Alzheimer's disease.