Astrocytes synthesize and secrete alpha 2-macroglobulin: differences between the regulation of alpha 2-macroglobulin synthesis in rat liver and brain
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J Bauer1, P J Gebicke-Haerter, U Ganter
1Medizinische Klinik, Freiburg, West Germany.
Abstract:
alpha 2-Macroglobulin (alpha 2M) is an important proteinase inhibitor both in the blood and in the interstitial space of many mammalian species. Recently, occurrence of alpha 2M in human and fetal rat brain has been reported. However, its cellular origin remained obscure. Here it will be shown that astroglial cells cultured from newborn rats synthesize and secrete alpha 2M. In addition to astrocyte primary cultures a rat astrocytoma cell line, C6-cells, also synthesize and secrete alpha 2M. In contrast to hepatocytes of the adult rat, where alpha 2M is expressed as an acute-phase protein and where glucocorticoids and monocyte-derived factors are required for its synthesis, alpha 2M synthesis in astrocytes of newborn rats is independent from both. It is therefore concluded that expression of alpha 2M is differently regulated in the liver of the adult rat and fetal or neonatal brain.
Insights
Astroglial cells in newborn rats synthesize alpha-2-macroglobulin (alpha 2M), a key proteinase inhibitor. This brain alpha 2M expression is independent of factors regulating its production in adult rat liver.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Alpha-2-macroglobulin (alpha 2M) is a crucial proteinase inhibitor found in mammalian blood and interstitial spaces.
- Recent studies have detected alpha 2M in the human and fetal rat brain, but its cellular source was unknown.
Purpose of the Study:
- To identify the cellular origin of alpha 2-macroglobulin (alpha 2M) in the developing rat brain.
- To investigate the regulation of alpha 2M synthesis in brain cells compared to liver cells.
Main Methods:
- Primary astrocyte cultures from newborn rats were used to study alpha 2M synthesis.
- A rat astrocytoma cell line (C6-cells) was also utilized to examine alpha 2M production.
- Alpha 2M synthesis in astrocytes was assessed for independence from glucocorticoids and monocyte-derived factors.
Main Results:
- Astroglial cells cultured from newborn rats were shown to synthesize and secrete alpha 2M.
- The rat astrocytoma cell line, C6-cells, also demonstrated the capacity to synthesize and secrete alpha 2M.
- Unlike adult rat hepatocytes, alpha 2M synthesis in neonatal rat astrocytes was independent of glucocorticoids and monocyte-derived factors.
Conclusions:
- Astroglial cells are a primary source of alpha 2-macroglobulin (alpha 2M) in the neonatal rat brain.
- The regulation of alpha 2M expression differs significantly between the adult rat liver and the neonatal rat brain.