Differential expression of individual complement regulators in the brain and choroid plexus

Membrane bound regulators of complement (C) control the system at key point s during activation. To determine whether C regulators were expressed in th e central nervous system, temporal cortex, and choroid plexus, tissues from eight adult humans were obtained at postmortem and surgery. Tissue was tak en fresh far total RNA isolation, snap freezing, or processing in paraffin wax for immunocytochemistry and in situ hybridization. Immunocytochemistry of temporal cortex using anti-CD59 stained microglia intensely; astrocytes and neurons weakly. Microglia wore unequivocally stained with anti-membrane cofactor protein (MCP) whereas staining on astrocytes and neurons was weak . Decay accelerating factor (DAF) was strongly expressed by microglia but w eakly by astrocytes. Neurons expressed neither DAF nor complement receptor 1 (CRI). GR1 was also absent on astrocytes and microglia. The choroid plexu s epithelium revealed intense apical staining with antibodies to CD59, less strongly with anti-MCP and weakly with anti-DAF. CR1 was detected only on phagocytic Kolmer cells in the choroid plexus. Reverse transcriptase-polyme rase chain reaction revealed CD59, MCP, and to a lesser degree, DAF mRNA bo th in the choroid plexus and temporal cortex. CR1 mRNA was detected in chor oid plexus samples only. Digoxigenin-UTP-labeled riboprobes to all four mem brane regulators were used for in situ hybridization. DAF, MCP, and CD59 mR NA were expressed by epithelial cells of the choroid plexus and CRI mRNA wa s found only in Kolmer cells. In the temporal cortex, MCP and CD59 mRNA wer e expressed by glia and at low level by neurons, but DAF was not detected. Previous studies have suggested that C produced in inflamed brains in condi tions such as Alzheimer's and Huntington's diseases can be specifically tox ic to neurons. The demonstration herein that neurons express only very low levels of CD59 and MCP and lack both CR1 and DAF might explain their suscep tibility to C damage.