Normal Physiology and Function

The morphology and branching patterns of microglial cells display heterogeneity between different brain regions. Microglia in gray matter tend to be ramified, with processes extending in all directions. Cells in the white matter are bipolar and often align their cyto-plasmic extensions in parallel, at right angles to nerve fiber bundles. Thus, the morphology of microglia adapts to the architecture of the brain region they populate, whereas their phenotype appears to be influenced by the chemical composition of the microenvironment. For example, MHC class Il-positive and CD4-positive microglia are localized mostly in the white matter of normal brain. Regions lacking a blood-brain barrier show microglia and microglia-like cells with a different phenotype, suggesting that serum proteins influence the phenotype.

The microglial plasma membrane contains a large number of receptor and adhesion molecules as well as a wide variety of enzymatic activities (Table III). Therefore, a large number of antibodies can be used to stain microglial cells. Microglia in the human brain can be visualized using analogous antibodies against typical macrophage surface receptors. In addition to the expression of Fc and complement receptors, other cell adhesion molecules are expressed constitutively on resting microglia in normal brain. Belonging to the integrin superfamily of adhesion molecules, these include typical lymphocytic antigens, such as lymphocyte function antigen (LFA), CD4 antigen, and leukocyte common antigen. B lymphocyte antigens are also present on human microglia. Thus, the microglial surface membrane bears molecules associated with white blood cells. It is well documented that the normal brain contains MHC antigens and that the principal MHC-expressing cell type is the microglial cell. The constitutive expression of MHC antigens in the brain is not limited to microglial cells, however; it also includes endothelial cells and certain cell types located in the wall of cerebral blood vessels. MHC antigen expression is considerably increased in pathologic conditions or after systemic administration of cytokines, such as interferon-g (IFN-g). The

Table III

Phenotypic Characteristics and Secretory Activity of Microglial Cellsa

Antigen expression Soluble mediator production

Resting Activated Cell specificity

Fc receptors

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