Abstract
Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.
Highlights
Multiple sclerosis (MS) involves the influx of leukocytes into the central nervous system (CNS) leading to demyelination and axonal degeneration
We found that sEMMPRIN levels in conditioned media of T-cells activated with anti-CD3 and anti-CD28 were significantly elevated (Fig 1)
Serum sEMMPRIN does not differ amongst subjects with different inflammatory conditions Earlier studies of amyotrophic lateral sclerosis (ALS) and systemic sclerosis had shown higher serum sEMMPRIN levels compared to healthy controls [13]
Summary
Multiple sclerosis (MS) involves the influx of leukocytes into the central nervous system (CNS) leading to demyelination and axonal degeneration. A large number of RRMS patients eventually transition to secondary progressive MS (SPMS) where disability accumulates without obvious clinical relapses. Another progressive form of MS, primary progressive MS (PPMS), is diagnosed in about 10–15% of patients and is characterized by steady loss of function from onset without obvious relapse activity. The expression of integrins and immunologlobulin (Ig) superfamily members is important for leukocyte migration across the vascular endothelium [4] In this context, the Extracellular Matrix Metalloproteinase Inducer (EMMPRIN, CD147), a type I transmembrane glycoprotein of the immunoglobulin (Ig) superfamily, seems crucial as it can interact with adhesion molecules including integrins [5, 6]. The upregulation of EMMPRIN in EAE and MS has pathological significance since the treatment of EAE mice with function blocking antiEMMPRIN antibodies reduced the number of perivascular cuffs and clinical severity [8, 10]
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