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Anti‐heat shock protein 90β antibodies decrease pre‐oligodendrocyte population in perinatal and adult cell cultures. Implications for remyelination in multiple sclerosis
Author(s) -
Cid Cristina,
ÁlvarezCermeño Jose C.,
Salinas Matilde,
Alcázar Alberto
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03371.x
Subject(s) - remyelination , oligodendrocyte , antibody , population , immunology , biology , heat shock protein , multiple sclerosis , complement membrane attack complex , complement system , myelin , medicine , neuroscience , biochemistry , central nervous system , environmental health , gene
Lesions in the CNS of patients with multiple sclerosis (MS) often fail to remyelinate, resulting in neurological dysfunction. A key factor seems to be the inefficiency of oligodendrocyte precursor cells (OPCs). We recently reported antibodies against heat shock protein 90β (Hsp90β) in MS patients that recognized the antigen on the OPC surface. This study investigates the mechanism and result of anti‐Hsp90β antibody attack. These antibodies induced OPC death in culture in a complement‐dependent fashion. Anti‐Hsp90β antibody‐induced, complement‐mediated OPC death only operated in these cells and caused a significant reduction in the number of O4‐positive pro‐oligodendrocytes (pre‐oligodendrocytes). Adult cultured OPCs also expressed Hsp90β on their cell surface and were attacked by anti‐Hsp90β antibodies leading to a significant decrease in the pre‐oligodendrocyte population. In the presence of low levels of anti‐Hsp90β antibody – i.e. in the range seen in the CSF of MS patients – the complement concentration was critical to reduce the pre‐oligodendrocyte population (via attack to OPCs). Higher concentrations of anti‐Hsp90β antibodies and complement became extinct the pre‐oligodendrocytes. Complement 1‐esterase inhibitor prevented these effects in the pre‐oligodendrocyte population. These findings demonstrate, for the first time in vitro , a feasible mechanism to decrease the production of new oligodendrocytes, thus limiting the possibility of remyelination.