title: P2Y12 expression and function in alternatively activated human microglia.
abstract: OBJECTIVE
  To investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation.
  
  
  METHODS
  We performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain.
  
  
  RESULTS
  We demonstrated that compared to resting and classically activated (M1) human microglia, P2Y12 expression is increased under alternatively activated (M2) conditions. In response to ADP, the endogenous ligand of P2Y12, M2 microglia have increased ligand-mediated calcium responses, which are blocked by selective P2Y12 antagonism. P2Y12 antagonism was also shown to decrease migratory and inflammatory responses in human microglia upon exposure to nucleotides that are released during CNS injury; no effects were observed in human monocytes or macrophages. In situ experiments confirm that P2Y12 is selectively expressed on human microglia and elevated under neuropathologic conditions that promote Th2 responses, such as parasitic CNS infection.
  
  
  CONCLUSIONS
  These findings provide insight into the roles of M2 microglia in the context of neuroinflammation and suggest a mechanism to selectively target a functionally unique population of myeloid cells in the CNS.
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Moore
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Ariel R
authors.initials: AR
authors.lastname: Ase
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Angham
authors.initials: A
authors.lastname: Kinsara
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Vijayaraghava T S
authors.initials: VT
authors.lastname: Rao
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Michell-Robinson
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Soo Yuen
authors.initials: SY
authors.lastname: Leong
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Oleg
authors.initials: O
authors.lastname: Butovsky
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Ludwin
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Séguéla
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: Division of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel
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