Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain

The Journal of Biological Chemistry
H Lee TiffanyP M Murphy

Abstract

Amyloid-beta, the pathologic protein in Alzheimer's disease, induces chemotaxis and production of reactive oxygen species in phagocytic cells, but mechanisms have not been fully defined. Here we provide three lines of evidence that the phagocyte G protein-coupled receptor (N-formylpeptide receptor 2 (FPR2)) mediates these amyloid-beta-dependent functions in phagocytic cells. First, transfection of FPR2, but not related receptors, including the other known N-formylpeptide receptor FPR, reconstituted amyloid-beta-dependent chemotaxis and calcium flux in HEK 293 cells. Second, amyloid-beta induced both calcium flux and chemotaxis in mouse neutrophils (which express endogenous FPR2) with similar potency as in FPR2-transfected HEK 293 cells. This activity could be specifically desensitized in both cell types by preincubation with a specific FPR2 agonist, which desensitizes the receptor, or with pertussis toxin, which uncouples it from G(i)-dependent signaling. Third, specific and reciprocal desensitization of superoxide production was observed when N-formylpeptides and amyloid-beta were used to sequentially stimulate neutrophils from FPR -/- mice, which express FPR2 normally. Potential biological relevance of these results to the ne...Continue Reading

References

Apr 30, 1992·Biochemical and Biophysical Research Communications·R D YeC G Cochrane
Dec 15, 1992·Biochemical and Biophysical Research Communications·J B DavisD Schubert
May 16, 1990·Biochemical and Biophysical Research Communications·F BoulayP Vignais
Jan 1, 1988·Alzheimer Disease and Associated Disorders·D E SchmechelA D Roses
Mar 15, 1994·Biochemical and Biophysical Research Communications·A KlegerisP L McGeer
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·D SchubertH Kimura
Jul 1, 1994·The Journal of Experimental Medicine·S FioreC N Serhan
Jan 1, 1994·Annual Review of Immunology·P M Murphy
May 30, 1994·Biochemical and Biophysical Research Communications·M DurstinP M Murphy
Dec 15, 1995·The Journal of Biological Chemistry·C CombadiereP M Murphy
Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·J A LondonJ S Pachter
Sep 1, 1996·Neurobiology of Aging·J RogersP McGeer
Jul 7, 1997·The Journal of Experimental Medicine·H L TiffanyP M Murphy
Aug 8, 1997·Biochemical and Biophysical Research Communications·Y LiuD Schubert
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·C Sturchler-PierratB Sommer
Aug 4, 1998·The Journal of Experimental Medicine·B M BradtN R Cooper
Sep 30, 1998·The European Journal of Neuroscience·J G SchulzU Dirnagl
Feb 17, 1999·The Journal of Experimental Medicine·J L GaoP M Murphy
Feb 26, 1999·The Journal of Biological Chemistry·H AliR Snyderman
Apr 24, 1999·Neuropathology and Applied Neurobiology·E Storey, R Cappai
Jun 11, 1999·The American Journal of Pathology·M StalderM Jucker

❮ Previous
Next ❯

Citations

Oct 29, 2002·Trends in Immunology·Yingying LeJi Ming Wang
Dec 15, 2011·European Journal of Human Genetics : EJHG·Anne Rovelet-LecruxUNKNOWN Investigators of the GMAJ project
May 15, 2003·The Journal of Biological Chemistry·Kiyoshi Itagaki, Carl J Hauser
Oct 14, 2008·Rejuvenation Research·Carl F FortinTàmàs Fülöp
Dec 25, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maren RautenbergAndreas Peschel
Feb 26, 2011·Molecular Pharmacology·Ana María Martín-MorenoMaría L de Ceballos
Jun 22, 2011·Journal of Innate Immunity·H Lee TiffanyPhilip M Murphy
Nov 18, 2011·Experimental & Molecular Medicine·Geon Ho BaeYoe-Sik Bae
Mar 15, 2014·Journal of Neuroinflammation·Deborah Doens, Patricia L Fernández
Nov 3, 2010·Neurochemical Research·Fabio CattaneoRosario Ammendola
Feb 26, 2016·Frontiers in Immunology·Enrica PietronigroGabriela Constantin
Feb 12, 2013·Cell Calcium·Bianca Brawek, Olga Garaschuk
Nov 19, 2014·Molecular Neurobiology·Valentina VillaTullio Florio
Oct 3, 2014·BioMed Research International·Alessandra Cadete MartiniGiles Alexander Rae
Aug 26, 2014·Cellular and Molecular Neurobiology·Yang Yu, Richard D Ye
Oct 11, 2008·Current Opinion in Pharmacology·Christopher D JohnJulia C Buckingham
Mar 18, 2017·Frontiers in Immunology·Enrica Caterina PietronigroGabriela Constantin
Nov 5, 2014·Journal of Medicinal Chemistry·Olivier Corminboeuf, Xavier Leroy
Apr 4, 2013·International Journal of Molecular Sciences·Fabio CattaneoRosario Ammendola
Mar 26, 2004·Glia·Jaroslava Ciesielski-TreskaMarie-France Bader
Oct 16, 2002·Glia·Thomas Möller
Sep 12, 2008·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Susan M YoungBruce S Edwards
Dec 22, 2004·The Journal of Biological Chemistry·Masato MoriguchiJohn J O'Shea
Sep 29, 2006·Glia·Katrin Färber, Helmut Kettenmann
Apr 30, 2011·Physiological Reviews·Helmut KettenmannAlexei Verkhratsky
Aug 17, 2004·Molecular Pharmacology·Masakatsu NanamoriRichard D Ye
Dec 5, 2019·Molecular Nutrition & Food Research·Changmo KimJeremy M Sivak
Nov 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H YazawaJ M Wang
Dec 18, 2002·The Journal of Biological Chemistry·Tomas DobranskyR Jane Rylett

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.