Expression of functional formyl peptide receptors by human astrocytoma cell lines

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.