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Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
The human astrocytoma cell line U373MG produces monocyte chemotactic protein (MCP)-1 upon stimulation with
1Institute of Neurology, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy.
Abstract:
Astrocytes associated with beta-amyloid (Abeta) accumulate in senile plaques of Alzheimer's disease (AD). To investigate the biological effects of Abeta/astrocyte interaction, we examined chemokine production by the human astrocytoma cell line U373MG stimulated with Abeta peptides. Northern blot analysis and specific immunoassays demonstrate that Abeta [1-42] and Abeta [25-35] induce mRNA expression and release of monocyte chemotactic protein (MCP)-1 but not of gamma-interferon inducible protein (IP)-10 by U373MG cells. The observation that Abeta induces astrocyte production of the potent microglia chemoattractant MCP-1 contributes to understanding mechanism of damage exerted by Abeta in AD senile plaques.
Insights
Beta-amyloid (Abeta) peptides stimulate astrocytes to produce monocyte chemotactic protein-1 (MCP-1). This finding helps explain how Abeta contributes to damage in Alzheimer's disease senile plaques.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Astrocytes, a type of glial cell, are found near beta-amyloid (Abeta) deposits in Alzheimer's disease (AD) senile plaques.
- The interaction between Abeta and astrocytes is crucial for understanding AD pathogenesis.
Purpose of the Study:
- To investigate the biological effects of Abeta/astrocyte interactions.
- To examine chemokine production by human astrocytoma cells stimulated with Abeta peptides.
Main Methods:
- Utilized the human astrocytoma cell line U373MG.
- Stimulated cells with Abeta [1-42] and Abeta [25-35] peptides.
- Employed Northern blot analysis and specific immunoassays to detect gene expression and protein release.
Main Results:
- Abeta [1-42] and Abeta [25-35] significantly induced mRNA expression and release of monocyte chemotactic protein-1 (MCP-1) in U373MG cells.
- The study found no induction of gamma-interferon inducible protein (IP)-10 by Abeta peptides in these cells.
- Abeta peptides trigger astrocytes to produce MCP-1, a chemoattractant for microglia.
Conclusions:
- Abeta peptides stimulate astrocytes to produce MCP-1.
- This astrocyte-derived MCP-1 may contribute to the recruitment of microglia and subsequent damage in Alzheimer's disease senile plaques.
- Understanding this mechanism provides insight into Abeta-mediated neuroinflammation in AD.
