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      Platelets Recognize Brain-Specific Glycolipid Structures, Respond to Neurovascular Damage and Promote Neuroinflammation

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          Abstract

          Platelets respond to vascular damage and contribute to inflammation, but their role in the neurodegenerative diseases is unknown. We found that the systemic administration of brain lipid rafts induced a massive platelet activation and degranulation resulting in a life-threatening anaphylactic-like response in mice. Platelets were engaged by the sialated glycosphingolipids (gangliosides) integrated in the rigid structures of astroglial and neuronal lipid rafts. The brain-abundant gangliosides GT1b and GQ1b were specifically recognized by the platelets and this recognition involved multiple receptors with P-selectin (CD62P) playing the central role. During the neuroinflammation, platelets accumulated in the central nervous system parenchyma, acquired an activated phenotype and secreted proinflammatory factors, thereby triggering immune response cascades. This study determines a new role of platelets which directly recognize a neuronal damage and communicate with the cells of the immune system in the pathogenesis of neurodegenerative diseases.

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          Author and article information

          Contributors
          Role: Editor
          Journal
          PLoS One
          PLoS ONE
          plos
          plosone
          PLoS ONE
          Public Library of Science (San Francisco, USA )
          1932-6203
          2013
          26 March 2013
          : 8
          : 3
          Affiliations
          [1 ]Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
          [2 ]Division of Neonatal-Perinatal Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
          [3 ]The Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, United States of America
          [4 ]School for Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
          Virginia Commonwealth University, United States of America
          Author notes

          Competing Interests: The authors have declared that no competing interests exist.

          Performed experiments and data analysis using Imaging Cytometry: NB. Conceived and designed the experiments: IS TV EDP. Performed the experiments: IS TV SCS NB EDP. Analyzed the data: IS TV SCS NB HLW EDP. Contributed reagents/materials/analysis tools: NB. Wrote the paper: IS HLW EDP.

          Article
          PONE-D-12-34759
          10.1371/journal.pone.0058979
          3608633
          23555611

          This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

          Page count
          Pages: 19
          Funding
          The work was supported in part by R01 NS071039-01A1 grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.
          Categories
          Research Article
          Biology
          Biochemistry
          Glycobiology
          Glycolipids
          Immunology
          Model Organisms
          Animal Models
          Mouse
          Neuroscience
          Mathematics
          Statistics
          Biostatistics
          Medicine
          Clinical Immunology
          Immunity
          Inflammation
          Immune Response
          Hematology
          Platelets
          Neurology
          Neurodegenerative Diseases

          Uncategorized

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