Expression of functional formyl peptide receptors by human astrocytoma cell lines.
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.
Le
Y
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Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, 21702-1201, Frederick, MD, USA.
Hu
J
J
Gong
W
W
Shen
W
W
Li
B
B
Dunlop
N M
NM
Halverson
D O
DO
Blair
D G
DG
Wang
J M
JM
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
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