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Open Access Research

A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and neurotoxicity: relevance to multiple sclerosis

Smriti M Agrawal, Claudia Silva, Janet Wang, Jade Pui-Wai Tong and V Wee Yong*

Author Affiliations

Departments of Clinical Neurosciences and Oncology, Hotchkiss Brain Institute and the, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada

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Journal of Neuroinflammation 2012, 9:64  doi:10.1186/1742-2094-9-64

Published: 5 April 2012

Abstract

Background

Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin) is an inducer of the expression of several matrix metalloproteinases (MMPs). We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE).

Methods

To improve upon EMMPRIN blockade, and to help unravel the biological functions of EMMPRIN in inflammatory disorders, we have developed several anti-EMMPRIN monoclonal antibodies.

Results

Of these monoclonal antibodies, a particular one, clone 10, was efficient in binding mouse and human cells using several methods of detection. The specificity of clone 10 was demonstrated by its lack of staining of EMMPRIN-null embryos compared to heterozygous and wild-type mouse samples. Functionally, human T cells activated with anti-CD3 and anti-CD28 elevated their expression of EMMPRIN and the treatment of these T cells with clone 10 resulted in decreased proliferation and matrix metalloproteinase- 9 (MMP-9) production. Activated human T cells were toxic to human neurons in culture and clone 10 pretreatment reduced T cell cytotoxicity correspondent with decrease of granzyme B levels within T cells. In vivo, EAE mice treated with clone 10 had a markedly reduced disease score compared to mice treated with IgM isotype control.

Conclusions

We have produced a novel anti-EMMPRIN monoclonal antibody that blocks several aspects of T cell activity, thus highlighting the multiple roles of EMMPRIN in T cell biology. Moreover, clone 10 reduces EAE scores in mice compared to controls, and has activity on human cells, potentially allowing for the testing of anti-EMMPRIN treatment not only in EAE, but conceivably also in MS.

Keywords:
Experimental autoimmune encephalomyelitis; Extracellular matrix metalloproteinase inducer; Function-blocking antibody; Matrix metalloproteinases; Multiple sclerosis; Neuroinflammation T cell proliferation; Neurotoxicity