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.
Highlights
The inflammation in the central nervous system (CNS) is a complex and understudied process, underlying numerous nosologies with a high socioeconomic impact worldwide
We performed a differential diagnosis of the clinical and laboratory features of the anaphylactic-like reaction induced by the brain lipid rafts and those of the thromboembolism induced by the i.v. administration of thrombin [26] (Table S3 in File S1; Video S1 and Video S2)
In this experiment we demonstrated that the administration of lipid rafts caused anaphylactic-like reaction that is symptomatically different form the thromboembolism induced by the injection of thrombin
Summary
The inflammation in the central nervous system (CNS) is a complex and understudied process, underlying numerous nosologies with a high socioeconomic impact worldwide. There is a growing body of knowledge demonstrating that platelets contribute to the inflammation in a number of pathologic processes including infection, atherosclerosis, and cancer metastasis [3,4,5,6,7]. The important role of platelets was reported in the pathogenesis of arthritis where they recognize the exposed collagen and produce microparticles upon activation [8]. A number of molecular structures which are exposed to the blood stream after the disruption of the endothelial cell integrity are recognized by platelets. These structures include von Willebrand factor, collagen, laminin, vitronectin and fibrinogen.
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