Platelets recognize brain-specific glycolipid structures, respond to neurovascular damage and promote neuroinflammation

• Published in: PloS one Vol. 8; no. 3; p. e58979
• Main Authors: Sotnikov, Ilya, Veremeyko, Tatyana, Starossom, Sarah C, Barteneva, Natalia, Weiner, Howard L, Ponomarev, Eugene D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.03.2013; Public Library of Science (PLoS)
• Subjects: Anaphylaxis; Anaphylaxis - immunology; Anaphylaxis - metabolism; Animals; Astrocytes - immunology; Astrocytes - metabolism; Biological Transport; Biology; Blood platelets; Blood Platelets - immunology; Blood Platelets - metabolism; Blood-Brain Barrier - metabolism; Brain; Brain - immunology; Brain - metabolism; Brain damage; Cardiac arrhythmia; Cascades; Cell Degranulation; Central nervous system; Central Nervous System - immunology; Central Nervous System - metabolism; Cerebrovascular Disorders - immunology; Cerebrovascular Disorders - metabolism; Degranulation; Disease; Disease Models, Animal; Dyspnea; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Gangliosides; Gangliosides - immunology; Glycolipids - immunology; Glycolipids - metabolism; Glycosphingolipids; Hospitals; Immune response; Immune system; Inflammation; Inflammation - immunology; Inflammation - metabolism; Lipid rafts; Lipids; Mathematics; Medical schools; Medicine; Membrane Microdomains - chemistry; Membrane Microdomains - immunology; Membrane Microdomains - metabolism; Mice; Neurodegenerative diseases; Neurological diseases; Neurons - immunology; Neurons - metabolism; P-selectin; Parenchyma; Pathogenesis; Phenotypes; Platelets; Protein Binding; Rafts; Receptors; Receptors, Cell Surface - metabolism; Rigid structures; Womens health; United States > US; Massachusetts
• DOI: 10.1371/journal.pone.0058979
• ISSN: 1932-6203

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.