Microglia-derived macrophages in early multiple sclerosis plaques.
One of the characteristics of ongoing demyelination in multiple sclerosis (MS) is the accumulation of lipid-laden macrophages in active lesions. Little is known about the source of these macrophages in the early stages of plaque evolution as microglial-derived and haematogenous macrophages share morphological characteristics and most cell surface antigens. A key issue in understanding the pathogenesis of MS is the reliable identification of phagocytes capable of degrading myelin and presenting 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 active MS plaques, defined as lesions with myelin-containing phagocytes but no obvious parenchymal myelin loss around these cells, were judged to originate from microglia as they exhibited nucleoside diphosphatase activity, a microglial marker. Only 4-15% of EBM11+ phagocytes in these lesions exhibited non-specific esterase activity, an enzyme marker for monocytes and macrophages. In contrast, 30-80% of EBM11+ phagocytes in more advanced active plaques with partial or complete myelin loss in the parenchyma were non-specific esterase+. Lysosomal enzyme acid phosphatase activity was strongly exhibited by 90% of phagocytes in all active plaques and there was a significant correlation between numbers of acid phosphatase+ cells and oil red O+ foamy macrophages. The results indicate that microglia are the main population of phagocytes in the early stages of demyelination and may play an important role in the pathogenesis of MS.
Li
H
H
Multiple Sclerosis Laboratory, Institute of Neurology, London, UK.
Cuzner
M L
ML
Newcombe
J
J
D000135:Acid Phosphatase / Q000378:metabolism; D000328:Adult; D000368:Aged; D001081:Apyrase / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D017628:Microglia / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology*
D000135:Acid Phosphatase; D001081:Apyrase