title: Expression of functional formyl peptide receptors by human astrocytoma cell lines.
abstract: Activation of astrocytes is important in the pathogenesis of a variety of diseases in the central nervous system, such as infection and neurodegeneration. We found that the bacterial chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLF) induced potent migration and Ca(2+) mobilization in human astrocytoma cell lines. The effect of fMLF was pertussis toxin-sensitive, suggesting the involvement of seven transmembrane, G protein-coupled receptor(s) for fMLF. Scatchard analyses revealed that astrocytoma cell lines express both high- and low-affinity binding sites for [3H]fMLF. RT-PCR confirmed the expression of transcripts of fMLF receptors, the high-affinity 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 activates FPRL1, increased secretion of IL-6 by astrocytoma cells. Our study demonstrates for the first time that FPR and FPRL1 expressed by astrocytoma cell lines are functional, and suggests a molecular basis for the involvement of these receptors in host defense in the brain.
authors.affiliation: Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, 21702-1201, Frederick, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Le
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: W
authors.initials: W
authors.lastname: Gong
authors.forename: W
authors.initials: W
authors.lastname: Shen
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: N M
authors.initials: NM
authors.lastname: Dunlop
authors.forename: D O
authors.initials: DO
authors.lastname: Halverson
authors.forename: D G
authors.initials: DG
authors.lastname: Blair
authors.forename: J M
authors.initials: JM
authors.lastname: Wang
mesh_terms: D001254:Astrocytoma; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C105101:FPR2 protein, human; D015850:Interleukin-6; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; D014316:Tritium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium