Remyelination-promoting antibodies activate distinct Ca2+ influx pathways in astrocytes and oligodendrocytes: relationship to the mechanism of myelin repair.
Our laboratory has identified mouse and human monoclonal antibodies that promote myelin repair in multiple models of demyelinating disease. We have proposed that these antibodies promote remyelination by directly activating central nervous system glia. Intracellular calcium concentration was monitored using a Fura2 ratiometric assay. Repair-promoting antibodies induced distinct Ca2+ signals in both astrocytes and oligodendrocytes. Astrocyte Ca2+ signaling is mediated by a phospholipase C-dependent pathway while oligodendrocyte Ca2+ signaling is mediated via AMPA-sensitive glutamate receptors. An antibody's ability to induce Ca2+ signals is statistically correlated with promotion of myelin repair. These findings support the hypothesis that remyelination-promoting antibodies are acting directly at the surface of glial cells to induce calcium-dependent physiologic reparative function.
Paz Soldán
M Mateo
MM
Program in Molecular Neuroscience, Mayo Medical and Graduate Schools, 200 First Street SW, Rochester, MN 55905, USA.
Warrington
Arthur E
AE
Bieber
Allan J
AJ
Ciric
Bogoljub
B
Van Keulen
Virginia
V
Pease
Larry R
LR
Rodriguez
Moses
M
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000954:Antigens, Surface / Q000187:drug effects / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D005904:Glial Fibrillary Acidic Protein; D018091:Receptors, AMPA; D002118:Calcium