IMMUNOHISTOCHEMICAL AND GENETIC-EVIDENCE OF MYELOPEROXIDASE INVOLVEMENT IN MULTIPLE-SCLEROSIS

The myeloperoxidase enzyme (MPG) is expressed specifically in myeloid cells and catalyzes the formation of hypochlorous acid and other cytot oxic oxidants. We previously reported that two alleles of MPO exist wh ich differ in promoter strength due to a base difference in an Alu-enc oded hormone response element. The present study shows that the higher expressing MPO genotype is overrepresented in early onset multiple sc lerosis in females, implicating MPO in this demyelinating disease. Con trary to the general conception that macrophages lack MPG, immunohisto chemical analysis shows that MPO is present in microglia/macrophages i n and around MS lesions as shown by colocalization with major histocom patibility antigens HLA-DR and phagocytized myelin. Also, MPO mRNA seq uences are detected in cDNA derived from isolated human adult microgli a. This is the first evidence that MPO is present in microglia/macroph ages at MS lesions, that MPO gene expression occurs in microglia and t hat MPO plays a role in MS pathogenesis as shown by the allelic disequ ilibrium in early onset disease. (C) 1997 Elsevier Science B.V.