title: Hemichannels Are Required for Amyloid β-Peptide-Induced Degranulation and Are Activated in Brain Mast Cells of APPswe/PS1dE9 Mice.
abstract: Mast cells (MCs) store an array of proinflammatory mediators in secretory granules that are rapidly released upon activation by diverse conditions including amyloid beta (Aβ) peptides. In the present work, we found a rapid degranulation of cultured MCs through a pannexin1 hemichannel (Panx1 HC)-dependent mechanism induced by Aβ25-35 peptide. Accordingly, Aβ25-35 peptide also increased membrane current and permeability, as well as intracellular Ca(2+) signal, mainly via Panx1 HCs because all of these responses were drastically inhibited by Panx1 HC blockers and absent in the MCs of Panx1(-/-) mice. Moreover, in acute coronal brain slices of control mice, Aβ25-35 peptide promoted both connexin 43 (Cx43)- and Panx1 HC-dependent MC dye uptake and histamine release, responses that were only Cx43 HC dependent in Panx1(-/-) mice. Because MCs have been found close to amyloid plaques of patients with Alzheimer's disease (AD), their distribution in brain slices of APPswe/PS1dE9 mice, a murine model of AD, was also investigated. The number of MCs in hippocampal and cortical areas increased drastically even before amyloid plaque deposits became evident. Therefore, MCs might act as early sensors of amyloid peptide and recruit other cells to the neuroinflammatory response, thus playing a critical role in the onset and progression of AD.
authors.affiliation: Departamento de Fisiología, Pontificia Universidad Catülica de Chile, Santiago, Chile, Instituto Milenio, Centro Interdisciplinario de Neurociencias de Valparaíso, Valparaíso, Chile, paharcha@gmail.com jsaez@bio.puc.cl.
authors.forename: Paloma A
authors.initials: PA
authors.lastname: Harcha
authors.affiliation: Departamento de Fisiología, Pontificia Universidad Catülica de Chile, Santiago, Chile.
authors.forename: Aníbal
authors.initials: A
authors.lastname: Vargas
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France, University Pierre et Marie Curie, 75005 Paris, France, and MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
authors.forename: Chenju
authors.initials: C
authors.lastname: Yi
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France, University Pierre et Marie Curie, 75005 Paris, France, and MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
authors.forename: Annette A
authors.initials: AA
authors.lastname: Koulakoff
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France, University Pierre et Marie Curie, 75005 Paris, France, and MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
authors.affiliation: Departamento de Fisiología, Pontificia Universidad Catülica de Chile, Santiago, Chile, Instituto Milenio, Centro Interdisciplinario de Neurociencias de Valparaíso, Valparaíso, Chile, paharcha@gmail.com jsaez@bio.puc.cl.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Sáez
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D015550:Cell Degranulation / Q000502:physiology; D004195:Disease Models, Animal; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)
keywords: Alzheimer's disease; amyloid peptide; degranulation; hemichannels; mast cells