Activation of astrocytes is important in the pathogenesis of a variety of d
iseases in the central nervous system, such as infection and neurodegenerat
ion. We found that the bacterial chemotactic peptide, N-formyl-methionyl-le
ucyl-phenylalanine (fMLF) induced potent migration and Ca2+ mobilization in
human astrocytoma cell lines. The effect of fMLF was pertussis toxin-sensi
tive, suggesting the involvement of seven transmembrane, G protein-coupled
receptor(s) for fMLF. Scatchard analyses revealed that astrocytoma cell Lin
es express both high- and low-affinity binding sites for [H-3]fMLF. RT-PCR
confirmed the expression of transcripts of fMLF receptors, the high-affinit
y FPR and the low-affinity FPRL1 by these cells. Both fMLF and F peptide, a
synthetic peptide domain of HIV-1 envelope protein which specifically acti
vates FPRL1, increased secretion of IL-6 by astrocytoma cells. Our study de
monstrates for the first time that FPR and FPRL1 expressed by astrocytoma c
ell lines are functional, and suggests a molecular basis for the involvemen
t of these receptors in host defense in the brain. (C) 2000 Elsevier Scienc
e B.V. All rights reserved.