Expression of complement C4 and C9 genes by human astrocytes.

Abstract

Evidence exists that complement activation is involved in the pathogenesis of Alzheimer's disease (AD). It has been previously demonstrated that central nervous system (CNS) resident cells can synthesize complement proteins. Two key proteins in the complement pathway are the complement C4 and C9 proteins. Using reverse transcription-polymerase chain reaction, ELISA, immunocytochemical and immunoblot techniques, we showed that primary human astrocytes constitutively expressed complement C4 mRNA and protein, and that this was increased when cells were treated with interferon-gamma, but inhibited when cells were treated with interleukin-1beta (IL-1beta). C4 immunoreactivity could be localized to GFAP-positive astrocytes when protein secretion was inhibited. These results indicated that astrocytes could be a source of complement C4 in the human CNS. In addition it was shown that stimulated astrocytes could also express complement C9 mRNA, though C9 protein was not detectable in culture supernatants.