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Galectin-3/MAC-2 in experimental allergic encephalomyelitis
1Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Abstract:
The removal of degenerating myelin by phagocytosis is central to pathogenesis and repair in traumatized and diseased nervous system. Galectin-3/MAC-2 is a differentiation and activation marker of murine and human monocytes/macrophages/microglia. Galectin-3/MAC-2, along with MAC-1 that mediates myelin phagocytosis, marks an in vivo activation state in macrophages, which are involved in myelin degeneration and phagocytosis in injured mouse peripheral nerves. In contrast, high levels of MAC-1 but extremely low levels of Galectin-3/MAC-2 are expressed in vivo in injured CNS where myelin degeneration and phagocytosis progress extremely slowly. The present study was aimed at testing whether an activation state marked by Galectin-3/MAC-2 is present in vivo in the CNS of EAE mice concomitant with autoimmune induced myelin degeneration and phagocytosis. EAE was inflicted by mouse spinal cord homogenate. Demyelination was assessed by light microscopy and Galectin-3/MAC-2, MAC-1, and F4/80 expression by immunocytochemistry. We presently document that Galectin-3/MAC-2 expression is up regulated, along with MAC-1 and F4/80, in spinal cords and optic nerves of EAE mice in areas of demyelination and myelin degeneration, in myelin phagocytosing microglia and macrophages. Copolymer 1 (Glatiramer acetate) suppresses EAE, demyelination, and Galectin-3/MAC-2 expression. EAE pathogenesis thus involves a state of activation in microglia and macrophages characterized by the expression Galectin-3/MAC-2 along with MAC-1. Furthermore, the in vivo responses to injury and autoimmune challenge in the CNS differ in the activation pattern of microglia and macrophages with regard to Galectin-3/MAC-2 expression and the corresponding occurrence of myelin degeneration and phagocytosis.
Insights
Galectin-3/MAC-2 marks activated microglia and macrophages involved in myelin removal during central nervous system autoimmune disease. This activation state, along with myelin phagocytosis, is suppressed by Copolymer 1 in experimental autoimmune encephalomyelitis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Phagocytosis of myelin is crucial for nervous system repair and disease pathogenesis.
- Galectin-3/MAC-2 is a marker for activated monocytes, macrophages, and microglia.
- Myelin phagocytosis in peripheral nerves involves MAC-1-expressing macrophages, unlike the slow degeneration in the central nervous system (CNS).
Purpose of the Study:
- To investigate the presence of Galectin-3/MAC-2 activation in the CNS during experimental autoimmune encephalomyelitis (EAE).
- To determine if Galectin-3/MAC-2 expression correlates with autoimmune-induced myelin degeneration and phagocytosis in EAE.
- To assess the effect of Copolymer 1 on EAE, demyelination, and Galectin-3/MAC-2 expression.
Main Methods:
- Induction of EAE in mice using mouse spinal cord homogenate.
- Assessment of demyelination via light microscopy.
- Immunocytochemical analysis of Galectin-3/MAC-2, MAC-1, and F4/80 expression in spinal cords and optic nerves.
Main Results:
- Galectin-3/MAC-2, MAC-1, and F4/80 expression were upregulated in demyelinated areas of the CNS in EAE mice.
- These markers were found on microglia and macrophages actively phagocytosing myelin.
- Copolymer 1 treatment reduced EAE severity, demyelination, and Galectin-3/MAC-2 expression.
Conclusions:
- EAE pathogenesis involves microglia and macrophage activation, characterized by Galectin-3/MAC-2 and MAC-1 expression, correlating with myelin degeneration and phagocytosis.
- CNS responses to injury and autoimmune challenges differ in microglia/macrophage activation patterns, specifically regarding Galectin-3/MAC-2 expression and myelin phagocytosis.
- Galectin-3/MAC-2 serves as a key marker for identifying activated phagocytic cells in the CNS during autoimmune demyelinating diseases.