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The blood-brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia
V H Perry1, P R Crocker, S Gordon
1Department of Pharmacology, University of Oxford, England.
Abstract:
In vitro the expression of a sialic acid-binding receptor on murine macrophages, sialoadhesin, is regulated by exposure to an inducing agent present in serum. We have used immunocytochemistry to examine the macrophage populations of the nervous system in order to test whether this serum inducing agent (SIA) also regulates sialoadhesin expression in vivo and whether plasma proteins may influence the phenotype of macrophages of the nervous system. Microglia, the resident macrophages of the central nervous system, reside behind the blood-brain barrier and do not express sialoadhesin. Microglia and macrophage populations in the cicumventricular organs, choroid plexus and leptomeninges are exposed to plasma proteins and some macrophages express sialoadhesin at these sites. Injury to the CNS, which damages the blood-brain barrier, induces sialoadhesin expression on a proportion of macrophages and microglia within the parenchyma. The expression of sialoadhesin matches the temporal and spatial distribution of the plasma extravasation into the brain parenchyma. These experiments show that exposure to SIA is necessary for sialoadhesin expression and lend further support to the idea that the phenotype of microglia is in part regulated by the presence of the blood-brain barrier.
Insights
Serum inducing agent (SIA) regulates sialoadhesin expression in the nervous system. The blood-brain barrier influences microglia phenotype, with SIA exposure necessary for sialoadhesin expression in vivo.
Area of Science:
- Neuroimmunology
- Macrophage Biology
- Central Nervous System Research
Background:
- Sialoadhesin expression on murine macrophages is regulated by serum inducing agents (SIA) in vitro.
- Microglia, the resident macrophages of the central nervous system, are located behind the blood-brain barrier and typically do not express sialoadhesin.
Purpose of the Study:
- To investigate if SIA regulates sialoadhesin expression in vivo within the nervous system.
- To determine if plasma proteins influence the phenotype of central nervous system macrophages.
Main Methods:
- Immunocytochemistry was used to examine macrophage populations in the murine nervous system.
- Sialoadhesin expression was assessed in relation to the blood-brain barrier and plasma protein exposure.
Main Results:
- Microglia within the central nervous system parenchyma do not express sialoadhesin.
- Macrophages in circumventricular organs, choroid plexus, and leptomeninges, exposed to plasma proteins, express sialoadhesin.
- Central nervous system injury, breaching the blood-brain barrier, induced sialoadhesin expression in parenchymal macrophages and microglia.
- Sialoadhesin expression correlated with plasma extravasation into the brain parenchyma.
Conclusions:
- Exposure to serum inducing agent (SIA) is essential for in vivo sialoadhesin expression.
- The blood-brain barrier plays a role in regulating the phenotype of microglia.
- Plasma proteins can influence the phenotype of macrophages within the nervous system.