Expression of Urokinase Plasminogen Activator Receptor on Monocytes from Patients with Relapsing-Remitting Multiple Sclerosis: Effect of Glatiramer Acetate (Copolymer 1)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which peripheral blood monocytes play an important role. We have previously reported that patients with chronic progressive MS (CPMS) have significantly increased numbers of circulating monocytes which express the urokinase plasminogen activator receptor (uPAR). In the present study, we examined the expression of uPAR on monocytes in patients with relapsing-remitting multiple sclerosis (RRMS) not currently participating in a clinical trial and in patients with RRMS who were enrolled in a double-blind multicenter clinical trial designed to examine the effect of glatiramer acetate (copolymer 1; Copaxone) on relapsing disease. Patients with CPMS have sustained high levels of circulating uPAR-positive (uPAR(+)) monocytes. In comparison, patients with RRMS displayed variable levels of circulating uPAR(+) monocytes. Mean values for uPAR in patients with RRMS were above those seen for controls but were not as high as those observed for patients with secondary progressive MS. Patients with RRMS in the clinical trial also had variable levels of monocyte uPAR. However, patients in the treatment group displayed lower levels following 2 years of treatment. In both placebo-treated and glatiramer acetate-treated patients, the percentage of circulating uPAR(+) monocytes, as well as the density of uPAR expressed per cell (mean linear fluorescence intensity), increased just prior to the onset of a clinically documented exacerbation. Values fell dramatically with the development of clinical symptoms. uPAR levels in all groups correlated with both clinical activity and severity. Results indicate that monocyte activation is impatient in MS and that glatiramer acetate may have a significant effect on monocyte activation in patients with RRMS

Magnetic brain stimulation upregulates adhesion and prevents EAE: MMP-2, ICAM-1, and VCAM-1 in the choroid plexus as a target

We are most thankful to Prof. Yehuda Shoenfeld, head of Autoimmunity Center, Sheba Hospital at Tel Aviv, University in Israel, for critical and constructive comments on the manuscript. Thanks to Prof. B. Reljin and N. Stepanic, School of Informational Technology, Universirty of Belgrade for contribution in molecular images and computing analysis. Authors gratefully acknowledge the repeated gifts of the magnetic beads for magnetic brain stimulation of rats presented by Institute for Nuclear Physics, Vincha, Belgrade. Clinical signs appearance and significant increases of ICAM-1 and MMP-2 expressions with the clusters of VCAM-1(+) immunoreactivity in the choroids plexus epithelium to transferred anti-myelin oligodendroglial antibodies into the third brain ventricle, indicate important role of choroids plexus in the induction of acute experimental autoimmune encephalomyelitis (EAE). Magnetic brain stimulation with AKMA micro-magnet flux density of 60 miliTesla, 5 mm in diameter, implanted upon the pineal gland (PG), immediately after antibody injection, significantly decreases the expression of MMP-2 and ICAM-1 in the choroids plexus of the rat brain and abruptly suppresses the induction of acute EAE