Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures
Identifieur interne : 001618 ( Main/Exploration ); précédent : 001617; suivant : 001619Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures
Auteurs : Mansoureh Hakimi [Canada] ; Thirumahal Selvanantham [Canada] ; Erika Swinton [Canada] ; Ruth F. Padmore [Canada] ; Youren Tong [États-Unis] ; Ghassan Kabbach [Canada] ; Katerina Venderova [Canada] ; Stephen E. Girardin [Canada] ; Dennis E. Bulman [Canada] ; Clemens R. Scherzer [États-Unis] ; Matthew J. Lavoie [États-Unis] ; Denis Gris [États-Unis] ; David S. Park [Canada] ; Jonathan B. Angel [Canada] ; Jie Shen [États-Unis] ; Dana J. Philpott [Canada] ; Michael G. Schlossmacher [Canada]Source :
- Journal of Neural Transmission [ 0300-9564 ] ; 2011.
English descriptors
- KwdEn :
- Animals, Antibody-Dependent Cell Cytotoxicity, Autophagy (genetics), B-Lymphocytes (metabolism), Cells, Cultured, Cytokines (metabolism), Enzyme-Linked Immunosorbent Assay (methods), Genetic Predisposition to Disease (genetics), Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Leukocytes (metabolism), Macrophages (metabolism), Mice, Mice, Transgenic, Mutation (genetics), Parkinson Disease (genetics), Parkinson Disease (immunology), Parkinson Disease (pathology), Protein-Serine-Threonine Kinases (genetics), Protein-Serine-Threonine Kinases (metabolism), RNA, Messenger (metabolism), T-Lymphocytes (metabolism), Up-Regulation (physiology).
- MESH :
- chemical , genetics : Protein-Serine-Threonine Kinases.
- chemical , metabolism : Cytokines, Protein-Serine-Threonine Kinases, RNA, Messenger.
- genetics : Autophagy, Genetic Predisposition to Disease, Mutation, Parkinson Disease.
- immunology : Parkinson Disease.
- metabolism : B-Lymphocytes, Leukocytes, Macrophages, T-Lymphocytes.
- methods : Enzyme-Linked Immunosorbent Assay.
- pathology : Parkinson Disease.
- physiology : Up-Regulation.
- Animals, Antibody-Dependent Cell Cytotoxicity, Cells, Cultured, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Mice, Mice, Transgenic.
Abstract
Sequence variants at or near the leucine-rich repeat kinase 2 (
Here, we report that full-length Lrrk2 is a relatively common constituent of human peripheral blood mononuclear cells (PBMC) including affinity-isolated, CD14+ monocytes, CD19+ B-cells, and CD4+ as well as CD8+ T-cells. Up to 25% of PBMC from healthy donors and up to 43% of CD14+ monocytes were stained by anti-Lrrk2 antibodies using cell sorting. PBMC lysates contained full-length (>260 kDa) and higher molecular weight Lrrk2 species. The expression of
We conclude that Lrrk2 is a constituent of many cell types in the immune system. Following the recognition of microbial structures, stimulated macrophages respond with increased
Url:
DOI: 10.1007/s00702-011-0653-2
PubMed: 21552986
PubMed Central: 3376651
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000907
- to stream Pmc, to step Curation: 000907
- to stream Pmc, to step Checkpoint: 000916
- to stream PubMed, to step Corpus: 000C20
- to stream PubMed, to step Curation: 000C20
- to stream PubMed, to step Checkpoint: 000C20
- to stream Ncbi, to step Merge: 000E77
- to stream Ncbi, to step Curation: 000E77
- to stream Ncbi, to step Checkpoint: 000E77
- to stream Main, to step Merge: 001686
- to stream Main, to step Curation: 001618
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Parkinson’s disease-linked <italic>LRRK2</italic>
is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures</title>
<author><name sortKey="Hakimi, Mansoureh" sort="Hakimi, Mansoureh" uniqKey="Hakimi M" first="Mansoureh" last="Hakimi">Mansoureh Hakimi</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Selvanantham, Thirumahal" sort="Selvanantham, Thirumahal" uniqKey="Selvanantham T" first="Thirumahal" last="Selvanantham">Thirumahal Selvanantham</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Immunology, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Swinton, Erika" sort="Swinton, Erika" uniqKey="Swinton E" first="Erika" last="Swinton">Erika Swinton</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Padmore, Ruth F" sort="Padmore, Ruth F" uniqKey="Padmore R" first="Ruth F." last="Padmore">Ruth F. Padmore</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Department of Ophthalmology, University of Ottawa Eye Institute and The Ottawa Hospital, Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Ophthalmology, University of Ottawa Eye Institute and The Ottawa Hospital, Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tong, Youren" sort="Tong, Youren" uniqKey="Tong Y" first="Youren" last="Tong">Youren Tong</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kabbach, Ghassan" sort="Kabbach, Ghassan" uniqKey="Kabbach G" first="Ghassan" last="Kabbach">Ghassan Kabbach</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Venderova, Katerina" sort="Venderova, Katerina" uniqKey="Venderova K" first="Katerina" last="Venderova">Katerina Venderova</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Girardin, Stephen E" sort="Girardin, Stephen E" uniqKey="Girardin S" first="Stephen E." last="Girardin">Stephen E. Girardin</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Immunology, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bulman, Dennis E" sort="Bulman, Dennis E" uniqKey="Bulman D" first="Dennis E." last="Bulman">Dennis E. Bulman</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Division of Neurology, The Ottawa Hospital; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, The Ottawa Hospital; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A7">Regenerative Medicine Program, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Regenerative Medicine Program, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R." last="Scherzer">Clemens R. Scherzer</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lavoie, Matthew J" sort="Lavoie, Matthew J" uniqKey="Lavoie M" first="Matthew J." last="Lavoie">Matthew J. Lavoie</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gris, Denis" sort="Gris, Denis" uniqKey="Gris D" first="Denis" last="Gris">Denis Gris</name>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Microbiology and Immunology, University of North Carolina; Chapel Hill, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina; Chapel Hill, NC</wicri:regionArea>
<wicri:noRegion>NC</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Angel, Jonathan B" sort="Angel, Jonathan B" uniqKey="Angel J" first="Jonathan B." last="Angel">Jonathan B. Angel</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Division of Infectious Diseases, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Infectious Diseases, Ottawa Hospital Research Institute, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shen, Jie" sort="Shen, Jie" uniqKey="Shen J" first="Jie" last="Shen">Jie Shen</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Philpott, Dana J" sort="Philpott, Dana J" uniqKey="Philpott D" first="Dana J." last="Philpott">Dana J. Philpott</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Immunology, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Division of Neurology, The Ottawa Hospital; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, The Ottawa Hospital; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21552986</idno>
<idno type="pmc">3376651</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376651</idno>
<idno type="RBID">PMC:3376651</idno>
<idno type="doi">10.1007/s00702-011-0653-2</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">000907</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000907</idno>
<idno type="wicri:Area/Pmc/Curation">000907</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000907</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000916</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000916</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">000C20</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000C20</idno>
<idno type="wicri:Area/PubMed/Curation">000C20</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000C20</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000C20</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C20</idno>
<idno type="wicri:Area/Ncbi/Merge">000E77</idno>
<idno type="wicri:Area/Ncbi/Curation">000E77</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000E77</idno>
<idno type="wicri:doubleKey">0300-9564:2011:Hakimi M:parkinson:s:disease</idno>
<idno type="wicri:Area/Main/Merge">001686</idno>
<idno type="wicri:Area/Main/Curation">001618</idno>
<idno type="wicri:Area/Main/Exploration">001618</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Parkinson’s disease-linked <italic>LRRK2</italic>
is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures</title>
<author><name sortKey="Hakimi, Mansoureh" sort="Hakimi, Mansoureh" uniqKey="Hakimi M" first="Mansoureh" last="Hakimi">Mansoureh Hakimi</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Selvanantham, Thirumahal" sort="Selvanantham, Thirumahal" uniqKey="Selvanantham T" first="Thirumahal" last="Selvanantham">Thirumahal Selvanantham</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Immunology, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Swinton, Erika" sort="Swinton, Erika" uniqKey="Swinton E" first="Erika" last="Swinton">Erika Swinton</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Padmore, Ruth F" sort="Padmore, Ruth F" uniqKey="Padmore R" first="Ruth F." last="Padmore">Ruth F. Padmore</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Department of Ophthalmology, University of Ottawa Eye Institute and The Ottawa Hospital, Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Ophthalmology, University of Ottawa Eye Institute and The Ottawa Hospital, Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tong, Youren" sort="Tong, Youren" uniqKey="Tong Y" first="Youren" last="Tong">Youren Tong</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kabbach, Ghassan" sort="Kabbach, Ghassan" uniqKey="Kabbach G" first="Ghassan" last="Kabbach">Ghassan Kabbach</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Venderova, Katerina" sort="Venderova, Katerina" uniqKey="Venderova K" first="Katerina" last="Venderova">Katerina Venderova</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Girardin, Stephen E" sort="Girardin, Stephen E" uniqKey="Girardin S" first="Stephen E." last="Girardin">Stephen E. Girardin</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Immunology, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bulman, Dennis E" sort="Bulman, Dennis E" uniqKey="Bulman D" first="Dennis E." last="Bulman">Dennis E. Bulman</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Division of Neurology, The Ottawa Hospital; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, The Ottawa Hospital; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A7">Regenerative Medicine Program, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Regenerative Medicine Program, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R." last="Scherzer">Clemens R. Scherzer</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lavoie, Matthew J" sort="Lavoie, Matthew J" uniqKey="Lavoie M" first="Matthew J." last="Lavoie">Matthew J. Lavoie</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gris, Denis" sort="Gris, Denis" uniqKey="Gris D" first="Denis" last="Gris">Denis Gris</name>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Microbiology and Immunology, University of North Carolina; Chapel Hill, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina; Chapel Hill, NC</wicri:regionArea>
<wicri:noRegion>NC</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Angel, Jonathan B" sort="Angel, Jonathan B" uniqKey="Angel J" first="Jonathan B." last="Angel">Jonathan B. Angel</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Division of Infectious Diseases, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Infectious Diseases, Ottawa Hospital Research Institute, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shen, Jie" sort="Shen, Jie" uniqKey="Shen J" first="Jie" last="Shen">Jie Shen</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Philpott, Dana J" sort="Philpott, Dana J" uniqKey="Philpott D" first="Dana J." last="Philpott">Dana J. Philpott</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Immunology, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neuroscience, Ottawa Hospital Research Institute; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Program in Neuroscience, Department of Cellular & Molecular Medicine, University of Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Division of Neurology, The Ottawa Hospital; Ottawa, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, The Ottawa Hospital; Ottawa, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Neural Transmission</title>
<idno type="ISSN">0300-9564</idno>
<idno type="eISSN">1435-1463</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibody-Dependent Cell Cytotoxicity</term>
<term>Autophagy (genetics)</term>
<term>B-Lymphocytes (metabolism)</term>
<term>Cells, Cultured</term>
<term>Cytokines (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay (methods)</term>
<term>Genetic Predisposition to Disease (genetics)</term>
<term>Humans</term>
<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term>
<term>Leukocytes (metabolism)</term>
<term>Macrophages (metabolism)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Mutation (genetics)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (immunology)</term>
<term>Parkinson Disease (pathology)</term>
<term>Protein-Serine-Threonine Kinases (genetics)</term>
<term>Protein-Serine-Threonine Kinases (metabolism)</term>
<term>RNA, Messenger (metabolism)</term>
<term>T-Lymphocytes (metabolism)</term>
<term>Up-Regulation (physiology)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein-Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Autophagy</term>
<term>Genetic Predisposition to Disease</term>
<term>Mutation</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>B-Lymphocytes</term>
<term>Leukocytes</term>
<term>Macrophages</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Enzyme-Linked Immunosorbent Assay</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Antibody-Dependent Cell Cytotoxicity</term>
<term>Cells, Cultured</term>
<term>Humans</term>
<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">Sequence variants at or near the leucine-rich repeat kinase 2 (<italic>LRRK2</italic>
) locus have been associated with susceptibility to three human conditions: Parkinson disease (PD), Crohn’s disease and leprosy. Because all three disorders represent complex diseases with evidence of inflammation, we hypothesized a role for <italic>LRRK2</italic>
in immune cell functions.</p>
<p id="P2">Here, we report that full-length Lrrk2 is a relatively common constituent of human peripheral blood mononuclear cells (PBMC) including affinity-isolated, CD14+ monocytes, CD19+ B-cells, and CD4+ as well as CD8+ T-cells. Up to 25% of PBMC from healthy donors and up to 43% of CD14+ monocytes were stained by anti-Lrrk2 antibodies using cell sorting. PBMC lysates contained full-length (>260 kDa) and higher molecular weight Lrrk2 species. The expression of <italic>LRRK2</italic>
in circulating leukocytes was confirmed by microscopy of human blood smears and in sections from normal midbrain and distal ileum. Lrrk2 reactivity was also detected in mesenteric lymph nodes and spleen (including in dendritic cells), but was absent in splenic mononuclear cells from <italic>lrrk2</italic>
-null mice, as expected. In cultured bone marrow-derived macrophages (BMDM) from mice we made three observations: (i) a predominance of higher molecular weight lrrk2; (ii) the reduction of autophagy marker LC3-II in <sup>R1441C</sup>
lrrk2-mutant cells (≥31%); and (iii) a significant up-regulation of <italic>lrrk2</italic>
mRNA (>4-fold) and protein after exposure to microbial structures including bacterial lipopolysaccharide and to lentiviral particles.</p>
<p id="P3">We conclude that Lrrk2 is a constituent of many cell types in the immune system. Following the recognition of microbial structures, stimulated macrophages respond with increased <italic>lrrk2</italic>
gene expression. In the same cells, lrrk2 appears to co-regulate autophagy, which is reduced in <sup>R1441C</sup>
lrrk2-mutant mice. A pattern recognition receptor-type function for <italic>LRRK2</italic>
could explain the locus association with Crohn’s disease and leprosy risk. We speculate that the role of Lrrk2 in immune cells may also be of relevance for the susceptibility to develop PD or its propagation.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>États-Unis</li>
</country>
<region><li>Ontario</li>
</region>
<settlement><li>Toronto</li>
</settlement>
<orgName><li>Université de Toronto</li>
</orgName>
</list>
<tree><country name="Canada"><noRegion><name sortKey="Hakimi, Mansoureh" sort="Hakimi, Mansoureh" uniqKey="Hakimi M" first="Mansoureh" last="Hakimi">Mansoureh Hakimi</name>
</noRegion>
<name sortKey="Angel, Jonathan B" sort="Angel, Jonathan B" uniqKey="Angel J" first="Jonathan B." last="Angel">Jonathan B. Angel</name>
<name sortKey="Bulman, Dennis E" sort="Bulman, Dennis E" uniqKey="Bulman D" first="Dennis E." last="Bulman">Dennis E. Bulman</name>
<name sortKey="Bulman, Dennis E" sort="Bulman, Dennis E" uniqKey="Bulman D" first="Dennis E." last="Bulman">Dennis E. Bulman</name>
<name sortKey="Girardin, Stephen E" sort="Girardin, Stephen E" uniqKey="Girardin S" first="Stephen E." last="Girardin">Stephen E. Girardin</name>
<name sortKey="Hakimi, Mansoureh" sort="Hakimi, Mansoureh" uniqKey="Hakimi M" first="Mansoureh" last="Hakimi">Mansoureh Hakimi</name>
<name sortKey="Kabbach, Ghassan" sort="Kabbach, Ghassan" uniqKey="Kabbach G" first="Ghassan" last="Kabbach">Ghassan Kabbach</name>
<name sortKey="Padmore, Ruth F" sort="Padmore, Ruth F" uniqKey="Padmore R" first="Ruth F." last="Padmore">Ruth F. Padmore</name>
<name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<name sortKey="Philpott, Dana J" sort="Philpott, Dana J" uniqKey="Philpott D" first="Dana J." last="Philpott">Dana J. Philpott</name>
<name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name>
<name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name>
<name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name>
<name sortKey="Selvanantham, Thirumahal" sort="Selvanantham, Thirumahal" uniqKey="Selvanantham T" first="Thirumahal" last="Selvanantham">Thirumahal Selvanantham</name>
<name sortKey="Swinton, Erika" sort="Swinton, Erika" uniqKey="Swinton E" first="Erika" last="Swinton">Erika Swinton</name>
<name sortKey="Venderova, Katerina" sort="Venderova, Katerina" uniqKey="Venderova K" first="Katerina" last="Venderova">Katerina Venderova</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Tong, Youren" sort="Tong, Youren" uniqKey="Tong Y" first="Youren" last="Tong">Youren Tong</name>
</noRegion>
<name sortKey="Gris, Denis" sort="Gris, Denis" uniqKey="Gris D" first="Denis" last="Gris">Denis Gris</name>
<name sortKey="Lavoie, Matthew J" sort="Lavoie, Matthew J" uniqKey="Lavoie M" first="Matthew J." last="Lavoie">Matthew J. Lavoie</name>
<name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R." last="Scherzer">Clemens R. Scherzer</name>
<name sortKey="Shen, Jie" sort="Shen, Jie" uniqKey="Shen J" first="Jie" last="Shen">Jie Shen</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001618 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001618 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Canada |area= ParkinsonCanadaV1 |flux= Main |étape= Exploration |type= RBID |clé= PMC:3376651 |texte= Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:21552986" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a ParkinsonCanadaV1
This area was generated with Dilib version V0.6.29. |