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In vivo properties of monocyte chemoattractant protein-1
1Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Journal of Leukocyte Biology
|November 19, 1997
Summary
Monocyte chemoattractant protein-1 (MCP-1) plays a role in inflammation. Transgenic mice showed MCP-1 can cause monocyte infiltration when expressed at low levels, supporting its role in diseases like rheumatoid arthritis.
Area of Science:
- Immunology
- Molecular Biology
- Pathogenesis
Background:
- Monocyte chemoattractant protein-1 (MCP-1) is known to attract monocytes, T lymphocytes, and NK cells in vitro.
- MCP-1 expression is observed in inflammatory conditions such as atherosclerosis, multiple sclerosis, and rheumatoid arthritis.
Purpose of the Study:
- To elucidate the in vivo functions of MCP-1.
- To investigate the role of MCP-1 in disease pathogenesis using transgenic mouse models.
Main Methods:
- Construction and analysis of transgenic mouse lines with varying MCP-1 expression patterns.
- Assessment of monocyte infiltration and susceptibility to intracellular pathogens in transgenic mice.
- Evaluation of MCP-1 serum levels and immune responses.
Main Results:
- High-level, widespread MCP-1 expression did not induce monocyte infiltration but increased susceptibility to Listeria and Mycobacterium infections.
- Localized, low-level MCP-1 expression driven by the insulin promoter resulted in monocyte infiltration in pancreatic islets.
- These findings suggest MCP-1's in vitro functions are replicated in vivo under specific expression conditions.
Conclusions:
- MCP-1's pro-inflammatory role in vivo is dependent on its expression level and anatomical localization.
- The study validates the use of MCP-1-deficient mice to further explore its contribution to disease.
- Understanding MCP-1's in vivo behavior is crucial for its therapeutic targeting in inflammatory diseases.