Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine microglial cells.
Receptors for the bacterial chemotactic peptide fMLP are implicated in inflammation and host defense against microbial infection. We investigated the expression and function of fMLPR in microglial cells, which share characteristics of mononuclear phagocytes and play an important role in proinflammatory responses in the CNS. The expression of the genes encoding formyl peptide receptor (FPR)1 and FPR2, the high- and low-affinity fMLPR, was detected in a murine microglial cell line N9, but these cells did not respond to chemotactic agonists known for these receptors. N9 cells incubated with bacterial LPS increased the expression of fMLPR genes and developed a species of specific, but low-affinity, binding sites for fMLP, in association with marked calcium mobilization and chemotaxis responses to fMLP in a concentration range that typically activated the low-affinity receptor FPR2. In addition, LPS-treated N9 cells were chemoattracted by two FPR2-specific agonists, the HIV-1 envelope-derived V3 peptide, and the 42 aa form of the amyloid beta peptide which is a pathogenic agent in Alzheimer's disease. Primary murine microglial cells also expressed FPR1 and FPR2 genes, but similar to N9 cells, exhibited FPR2-mediated activation only after LPS treatment. In contrast to its effect on the function of FPR2, LPS reduced N9 cell binding and biological responses to the chemokine stromal cell-derived factor-1alpha. Thus, LPS selectively modulates the function of chemoattractant receptors in microglia and may promote host response in inflammatory diseases in the CNS.
Cui
You-Hong
YH
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute, Building 560, Frederick, MD 21702, USA.
Le
Yingying
Y
Gong
Wanghua
W
Proost
Paul
P
Van Damme
Jo
J
Murphy
William J
WJ
Wang
Ji Ming
JM
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D020806:Central Nervous System Bacterial Infections / Q000276:immunology; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000276:immunology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D020033:Protein Isoforms / Q000819:agonists / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D018000:Receptors, Peptide / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
D002630:Chemotactic Factors; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium