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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2013

Open Access 01-12-2013 | Research

Inflammation induces neuro-lymphatic protein expression in multiple sclerosis brain neurovasculature

Authors: Ganta Vijay Chaitanya, Seiichi Omura, Fumitaka Sato, Nicholas E Martinez, Alireza Minagar, Murali Ramanathan, Bianca Weinstock Guttman, Robert Zivadinov, Ikuo Tsunoda, Jonathan S Alexander

Published in: Journal of Neuroinflammation | Issue 1/2013

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Abstract

Background

Multiple sclerosis (MS) is associated with ectopic lymphoid follicle formation. Podoplanin+ (lymphatic marker) T helper17 (Th17) cells and B cell aggregates have been implicated in the formation of tertiary lymphoid organs (TLOs) in MS and experimental autoimmune encephalitis (EAE). Since podoplanin expressed by Th17 cells in MS brains is also expressed by lymphatic endothelium, we investigated whether the pathophysiology of MS involves inductions of lymphatic proteins in the inflamed neurovasculature.

Methods

We assessed the protein levels of lymphatic vessel endothelial hyaluronan receptor and podoplanin, which are specific to the lymphatic system and prospero-homeobox protein-1, angiopoietin-2, vascular endothelial growth factor-D, vascular endothelial growth factor receptor-3, which are expressed by both lymphatic endothelium and neurons. Levels of these proteins were measured in postmortem brains and sera from MS patients, in the myelin proteolipid protein (PLP)-induced EAE and Theiler’s murine encephalomyelitis virus (TMEV) induced demyelinating disease (TMEV-IDD) mouse models and in cell culture models of inflamed neurovasculature.

Results and conclusions

Intense staining for LYVE-1 was found in neurons of a subset of MS patients using immunohistochemical approaches. The lymphatic protein, podoplanin, was highly expressed in perivascular inflammatory lesions indicating signaling cross-talks between inflamed brain vasculature and lymphatic proteins in MS. The profiles of these proteins in MS patient sera discriminated between relapsing remitting MS from secondary progressive MS and normal patients. The in vivo findings were confirmed in the in vitro cell culture models of neuroinflammation.
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Metadata
Title
Inflammation induces neuro-lymphatic protein expression in multiple sclerosis brain neurovasculature
Authors
Ganta Vijay Chaitanya
Seiichi Omura
Fumitaka Sato
Nicholas E Martinez
Alireza Minagar
Murali Ramanathan
Bianca Weinstock Guttman
Robert Zivadinov
Ikuo Tsunoda
Jonathan S Alexander
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-10-125

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