title: Complement C5a receptor-mediated signaling may be involved in neurodegeneration in Alzheimer's disease.
abstract: In our earlier results, we demonstrated that cells expressing the complement C5aR are vulnerable since abnormal activation of C5aR caused apoptosis of these cells. In this study, we demonstrate that activation of C5aR by antisense homology box (AHB) peptides synthesized in multiple antigenic peptide form and representing putative interaction sites of the C5a/C5aR evoked calcium influx in TGW neuroblastoma cells. Dose-dependent inhibition of the response was found when the cells were pretreated with C5a, suggesting that C5aR was involved in this process. In addition, pretreatment with monomeric forms of the AHB peptides resulted in attenuation of the calcium signals, supporting the idea of the role of C5aR in this process. Cells of a neuron-rich primary culture and pyramidal cells of rat brain slices also responded to the AHB peptide activation with an increase in the intracellular calcium level, showing that calcium metabolism might be affected in these cells. TUNEL staining demonstrated that C5aR-mediated apoptosis could be induced both in cells of the primary culture as well as in cortical pyramidal neurons of the rat brain. In addition, we investigated expression of C5aR in the hippocampal and cortical neurons of human brains of healthy and demented patients using two anti-human C5aR Abs. Pyramidal cells of the hippocampus and cortex and granular cells of the hippocampus were immunopositive on staining. Although staining was also positive in the vascular dementia brain, it disappeared in the brain with Alzheimer's disease. These results provide further support that C5aR may be involved in neurodegeneration.
authors.affiliation: Department of Molecular Biology, Nagoya City University School of Medicine, Nagoya, Japan.
authors.forename: Imre
authors.initials: I
authors.lastname: Farkas
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Takahashi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Fukuda
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.forename: Lajos
authors.initials: L
authors.lastname: Baranyi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tateyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Okada
authors.forename: Hidechika
authors.initials: H
authors.lastname: Okada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001923:Brain Chemistry / Q000276:immunology; D020013:Calcium Signaling / Q000276:immunology; D002478:Cells, Cultured; D015936:Complement C5a / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D005456:Fluorescent Dyes; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C049925:fura-2-am; D015936:Complement C5a; D016257:Fura-2