Cunningham, M. , McGonigal, R. , Meehan, G. R. , Barrie, J. A., Yao, D., Halstead, S. K. and Willison, H. J. (2016) Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis. Brain, 139(6), pp. 1657-1665. (doi: 10.1093/brain/aww056) (PMID:27017187) (PMCID:PMC4892750)
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Abstract
In axonal forms of Guillain-Barré syndrome, anti-ganglioside antibodies bind gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-ganglioside antibodies from the cell surface so rapidly that antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating antibody levels. Remarkably, systemically delivered anti-ganglioside antibody in mice was so avidly cleared from the circulation by endocytosis at ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-ganglioside antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-ganglioside antibodies, and potentially other ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Halstead, Dr Susan and Barrie, Mrs Jennifer and Willison, Professor Hugh and McGonigal, Dr Rhona and Cunningham, Dr Madeleine and Yao, Dr Denggao and Meehan, Dr Gavin |
| Authors: | Cunningham, M., McGonigal, R., Meehan, G. R., Barrie, J. A., Yao, D., Halstead, S. K., and Willison, H. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Brain |
| Publisher: | Oxford University Press |
| ISSN: | 0006-8950 |
| ISSN (Online): | 1460-2156 |
| Published Online: | 26 March 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in Brain 139(6): 1657-1665 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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