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 ne rvous 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 clini cal trial and in patients with RRMS who were enrolled in a double-blind mul ticenter clinical trial designed to examine the effect of glatiramer acetat e (copolymer 1; Copaxone) on relapsing disease. Patients with CPMS have sus tained high levels of circulating uPAR-positive (uPAR(+)) monocytes. In com parison, patients with RRMS displayed variable levels of circulating uPAR() monocytes. Mean values for uPAR in patients with RRMS were above those se en for controls but were not as high as those observed for patients with se condary progressive MS. Patients with RRMS in the clinical trial also had v ariable levels of monocyte uPAR. However, patients in the treatment group d isplayed lower levels following 2 years of treatment. In both placebo-treat ed and glatiramer acetate-treated patients, the percentage of circulating u PAR(+) monocytes, as well as the density of uPAR expressed per cell (mean l inear fluorescence intensity), increased just prior to the onset of a clini cally documented exacerbation. Values fell dramatically with the developmen t of clinical symptoms. uPAR levels in all groups correlated with both clin ical activity and severity. Results indicate that monocyte activation is im patient in MS and that glatiramer acetate may have a significant effect on monocyte activation in patients with RRMS.