[Analysis of HAM rat disease with HTLV-I infection, an animal model for HAM/TSP in human-immunohistochemical, immuno-electron microscopic and flow cytometrical analyses of microglia/macrophages in the affected spinal cord].
HAM rat disease is a demyelinating disease in the spinal cord and peripheral nerve of WKAH rats with HTLV-I infection and has been described as an animal model for human T lymphocyte virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in humans. The histopathological characteristic in the affected lesions is a vacuolar myelopathy, with the apoptosis of oligodendrocytes and the massive infiltration of microglia/macrophage lineage cells. To investigate the pathogenetic role of the infiltrating microglias/macrophages in the lesion, the author carried out chronological analyses with immunohistochemistry, immuno-electron microscopy and flow cytometry on the spinal cord specimens of HAM rats. Many OX-42 positive cells were identified as microglias either irregular or plump in shape. Both MHC Class II and LFA-1 expressions were increased in these cells, suggesting they were activated in the lesion. Moreover, many microglias/macrophages showed PCNA positivity, indicating they proliferated locally. Some apoptotic microglias/macrophages were evidenced by immuno-electron microscopy. Flow cytometrical analysis revealed that the majority of the infiltrating cells in the affected lesion was originated from resident microglias, and macrophages from the blood stream appeared to be minimum. Collective evidence suggests that the activated and proliferated resident microglias with HTLV-I infection may play a critical role in the disease course through the production of cytotoxic factors such as TNF-alpha.
First Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
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Morita
D000818:Animals; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D015493:Paraparesis, Tropical Spastic / Q000209:etiology / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha