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Journal of Neuroinflammation

, 10:895

First Online: 14 October 2013Received: 10 July 2013Accepted: 24 September 2013


BackgroundMultiple 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.

MethodsWe 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 conclusionsIntense 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.

KeywordsProx-1 Angiopoietin-2 VEGFR-3 VEGF-D LYVE-1 Podoplanin-D2-40 Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-10-125 contains supplementary material, which is available to authorized users.

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Autor: Ganta Vijay Chaitanya - Seiichi Omura - Fumitaka Sato - Nicholas E Martinez - Alireza Minagar - Murali Ramanathan - Bianca


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