Galectin-3/MAC-2 in experimental allergic encephalomyelitis.
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.
Reichert
F
F
Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Rotshenker
S
S
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis / Q000378:metabolism*; D003433:Crosses, Genetic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D037502:Galectin 3; D006801:Humans; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009186:Myelin Sheath / Q000473:pathology; D009410:Nerve Degeneration; D009900:Optic Nerve / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000943:Antigens, Differentiation; D037502:Galectin 3; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; C036763:monocyte-macrophage differentiation antigen