MONOCYTE ACTIVATION ANTIGENS IN MULTIPLE SCLEROSIS

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Exposure of human peripheral blood monocytes to bacterial products, phorbol esters, cyclic adenosine monophosphate (cAMP) and cAMP agonists stimulate the surface expression of a membrane activation antigen, the glycoprotein Mo3. Mo3 is recognized by two monoclonal antibodies Mo3e (IgM) and Mo3f (IgG). Surface expression of Mo3 is barely detectable on nonstimulated monocytes, but is expressed in high density on stimulated monocytes and monocytes found in inflammatory tissue. We have found increased expression of Mo3 on circulating monocytes from patients with chronic progressive multiple sclerosis (CPMS) and relapsing remitting MS (RRMS). We have not found increased surface Mo3 (sMo3) in any other disease control group tested. Preliminary studies indicate that Mo3 may be the urokinase plasminogen activator receptor and may have a role in migration inhibition factor (MIF) function. Thus, Mo3+ monocytes may be primed for migration from the blood into the tissue. That MS monocytes express increased sMo3 suggests that in vivo stimulation of monocytes is an ongoing process. We propose in this application to complete clinical correlations in aim #1; to examine whether MS Mo3+ monocytes express other phenotypic and functional correlates of activation in aim #2; to examine Mo3 gene expression using Mo3 cDNA in aim #3.