title: Regulation of macrophage motility by the water channel aquaporin-1: crucial role of M0/M2 phenotype switch.
abstract: The water channel aquaporin-1 (AQP1) promotes migration of many cell types. Although AQP1 is expressed in macrophages, its potential role in macrophage motility, particularly in relation with phenotype polarization, remains unknown. We here addressed these issues in peritoneal macrophages isolated from AQP1-deficient mice, either undifferentiated (M0) or stimulated with LPS to orientate towards pro-inflammatory phenotype (classical macrophage activation; M1). In non-stimulated macrophages, ablation of AQP1 (like inhibition by HgCl2) increased by 2-3 fold spontaneous migration in a Src/PI3K/Rac-dependent manner. This correlated with cell elongation and formation of lamellipodia/ruffles, resulting in membrane lipid and F4/80 recruitment to the leading edge. This indicated that AQP1 normally suppresses migration of resting macrophages, as opposed to other cell types. Resting Aqp1-/- macrophages exhibited CD206 redistribution into ruffles and increased arginase activity like IL4/IL13 (alternative macrophage activation; M2), indicating a M0-M2 shift. In contrast, upon M1 orientation by LPS in vitro or peritoneal inflammation in vivo, migration of Aqp1-/- macrophages was reduced. Taken together, these data indicate that AQP1 oppositely regulates macrophage migration, depending on stimulation or not by LPS, and that macrophage phenotypic and migratory changes may be regulated independently of external cues.
authors.affiliation: CELL Unit, de Duve Institute (DDUV), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Donatienne
authors.initials: D
authors.lastname: Tyteca
authors.affiliation: Pôle de Néphrologie (NEFR), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain, Brussels, Belgium; Division of Nephrology, Nagasaki University, Nagasaki, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nishino
authors.affiliation: Pôle de Néphrologie (NEFR), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Huguette
authors.initials: H
authors.lastname: Debaix
authors.affiliation: CELL Unit, de Duve Institute (DDUV), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Der Smissen
authors.affiliation: CELL Unit, de Duve Institute (DDUV), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Francisca
authors.initials: F
authors.lastname: N'Kuli
authors.affiliation: CELL Unit, de Duve Institute (DDUV), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Delia
authors.initials: D
authors.lastname: Hoffmann
authors.affiliation: Pôle de Néphrologie (NEFR), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Cnops
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Rabolli
authors.affiliation: Inflammation Research Center, VIB, Department of Biomedical Molecular Biology, University of Ghent, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: van Loo
authors.affiliation: Inflammation Research Center, VIB, Department of Biomedical Molecular Biology, University of Ghent, Ghent, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Huaux
authors.affiliation: Pôle de Néphrologie (NEFR), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: CELL Unit, de Duve Institute (DDUV), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D001119:Arginase / Q000378:metabolism; D002465:Cell Movement; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051398:Aquaporin 1; D001119:Arginase; D007378:Interleukins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D019869:Phosphatidylinositol 3-Kinases; D011956:Receptors, Cell Surface; D020744:rac GTP-Binding Proteins; D019061:src-Family Kinases; C496021:Aqp1 protein, mouse