MICROGLIA-DERIVED MACROPHAGES IN EARLY MULTIPLE-SCLEROSIS PLAQUES

One of the characteristics of ongoing demyelination in multiple sclero sis (MS) is the accumulation of lipid-laden macrophages in active lesi ons. Little is known about the source of these macrophages in the earl y stages of plaque evolution as microglial-derived and haematogenous m acrophages share morphological characteristics and most cell surface a ntigens. A key issue in understanding the pathogenesis of MS is the re liable identification of phagocytes capable of degrading myelin and pr esenting autoantigen to T cells at the onset of demyelination, Using a combination of histochemistry and immunocytochemistry, an average of 60% of EBM11+ phagocytes (EMBII is a pan-macrophage marker) in early a ctive MS plaques, defined as lesions with myelin-containing phagocytes but no obvious parenchymal myelin loss around these cells, were judge d to originate from microglia as they exhibited nucleoside diphosphata se activity, a microglial marker, Only 4-15% of EBM11(+) phagocytes in these lesions exhibited non-specific esterase activity, an enzyme mar ker for monocytes and macrophages. In contrast, 30-80% of EBM11(+) pha gocytes in more advanced active plaques with partial or complete myeli n loss in the parenchyma were nonspecific esterase(+). Lysosomal enzym e acid phosphatase activity was strongly exhibited by 90% of phagocyte s in all active plaques and there was a significant correlation betwee n numbers of acid phosphatase(+) cells and oil red 0(+) foamy macropha ges. The results indicate that microglia are the main population of ph agocytes in the early stages of demyelination and may play an importan t role in the pathogenesis of MS.