Expression of citrullinated proteins in murine experimental autoimmune encephalomyelitis
| Autor: | Thiagarajan Sambandam, Anthony P. Nicholas, Scott R. Barnum, Joshua D. Echols |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Pathology
medicine.medical_specialty Encephalomyelitis Autoimmune Experimental Time Factors Encephalomyelitis Blotting Western Central nervous system Fluorescent Antibody Technique Biology Myelin oligodendrocyte glycoprotein Mice immune system diseases Glial Fibrillary Acidic Protein medicine Animals Glycoproteins Cerebral Cortex Glial fibrillary acidic protein General Neuroscience Multiple sclerosis Experimental autoimmune encephalomyelitis Antibodies Monoclonal Citrullination Myelin Basic Protein medicine.disease Peptide Fragments Myelin basic protein Mice Inbred C57BL medicine.anatomical_structure Spinal Cord nervous system Immunology biology.protein Citrulline Female Myelin-Oligodendrocyte Glycoprotein |
| Zdroj: | The Journal of Comparative Neurology. 486:254-266 |
| ISSN: | 1096-9861 0021-9967 |
| DOI: | 10.1002/cne.20527 |
| Popis: | In this study, we demonstrate for the first time the immunohistochemical expression of citrullinated proteins in the central nervous system (CNS) of mice with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). By using an established monoclonal antibody (F95) against natural and synthetic citrullinated proteins (Nicholas and Whitaker [2002] Glia 37:328-336), numerous, small, previously unrecognized "patches" of citrullinated proteins were discovered throughout EAE brains, whereas EAE spinal cords showed similar but much larger lesions. On dual color immunofluorescence, these lesions were found to contain citrullinated myelin basic protein (MBP) and were surrounded by astrocytes immunoreactive for both glial fibrillary acidic protein (GFAP) and F95. These lesions became evident about the time when EAE mice became symptomatic and increased in size and number with increasing disease severity. In some sections of spinal cord but not brains of severely debilitated EAE mice, a widespread gliotic response was seen, with astrocytes containing citrullinated GFAP spread throughout the gray and white matter. Western blot analysis of acidic proteins from the brains and spinal cords of EAE mice had higher levels of multiple citrullinated GFAP isoforms compared with controls, with more F95-positive bands in the EAE brains vs. spinal cords. These results raise the possibility that citrullination of both GFAP and MBP may contribute to the pathophysiology of EAE and that the brains of EAE mice may contain more pathology than previously realized. |
| Databáze: | OpenAIRE |
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