Evidence exists that complement activation is involved in the pathogen
esis of Alzheimer's disease (AD). It has been previously demonstrated
that central nervous system (CNS) resident cells can synthesize comple
ment proteins. Two key proteins in the complement pathway are the comp
lement C4 and C9 proteins. Using reverse transcription-polymerase chai
n reaction, ELISA, immunocytochemical and immunoblot techniques, we sh
owed that primary human astrocytes constitutively expressed complement
C4 mRNA and protein, and that this was increased when cells were trea
ted with interferon-gamma, but inhibited when cells were treated with
interleukin-1 beta (IL-1 beta). C4 immunoreactivity could be localized
to GFAP-positive astrocytes when protein secretion was inhibited. The
se results indicated that astrocytes could be a source of complement C
4 in the human CNS. In addition it was shown that stimulated astrocyte
s could also express complement C9 mRNA, though C9 protein was not det
ectable in culture supernatants. (C) 1998 Elsevier Science B.V. All ri
ghts reserved.