The role of Galectin-3/MAC-2 in the activation of the innate-immune function of phagocytosis in microglia in injury and disease.
Microglia are a self-sustained population of immune/myeloid cells present throughout the central nervous system (CNS). Microglia are in a "resting" state in the normal adult CNS. They turn "active" in injury and disease (e.g., trauma, neurodegeneration, and infection). Activated microglia can be beneficial as well as detrimental/neurotoxic. The innate-immune function of phagocytosis of tissue debris, neurotoxic factor, and pathogens is a beneficial function of microglia. The current manuscript reviews the role of Galectin-3 (known also as MAC-2; Galectin-3/MAC-2) in the activation of the phagocytosis of degenerated myelin that is mediated by complement receptor-3 (known also as MAC-1; CD11b/CD18; alphaMbeta2 integrin) and SRA (scavenger receptor-AI/II). Observations suggest that Galectin-3/MAC-2 may act as a molecular switch that activates phagocytosis by up-regulating and prolonging KRas-GTP-dependent PI3K (phosphatidylinositol 3-kinase) activity. A similar mechanism may regulate the phagocytosis of other tissue debris, neurotoxic factors and pathogens in neurodegenerative and infectious diseases.
Rotshenker
Shlomo
S
Department of Medical Neurobiology, IMRIC, Hebrew University-Hadassah Medical School and the Eric Roland Center for Neurodegenerative Diseases, P.O.B. 12272, Jerusalem 91120, Israel. shlomor@ekmd.huji.ac.il
D039481:CD11b Antigen / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D037502:Galectin 3 / Q000276:immunology*; D007113:Immunity, Innate; D017628:Microglia / Q000276:immunology*; D009186:Myelin Sheath / Q000378:metabolism; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology; D009422:Nervous System Diseases / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology*; D051117:Scavenger Receptors, Class A / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology
D039481:CD11b Antigen; D037502:Galectin 3; D051117:Scavenger Receptors, Class A