Oligodendrocytes and oligodendrocyte/type-2 astrocyte progenitor cells of adult rats are specifically susceptible to the lytic effects of complement in absence of antibody.
The central nervous system of individuals with multiple sclerosis contains lesions specifically characterized by breakdown of myelin sheaths associated with a general failure of repair of demyelinating damage. The cause of myelin breakdown is unknown. Although immune mechanisms have been implicated in this breakdown, no convincing demonstrations of specific immune reaction against myelin have yet been provided in multiple sclerosis patients. Similarly, the cellular biological mechanisms which underlie the failure of myelin repair are unknown. We have found that (i) oligodendrocytes, the cells that produce myelin sheaths in the central nervous system, and (ii) oligodendrocyte/type-2 astrocyte (O/2A) progenitor cells derived from optic nerves of adult rats bind and activate complement in the absence of antibody in vitro, leading to destruction of these cells. Susceptibility to antibody-independent lysis by complement was a cell-type-specific trait of oligodendrocytes and adult O/2A progenitors and was not shared by perinatal O/2A progenitors, type-2 astrocytes, type-1 astrocytes, meningeal cells, or Schwann cells. We suggest that the susceptibility of oligodendrocytes and adult O/2A progenitor cells to complement-induced lysis, combined with other specific properties of adult O/2A progenitors, are consistent with--and may be a contributing factor--both in the generation of demyelinating lesions in multiple sclerosis and also in the failure of these lesions to be successfully repaired in adult multiple sclerosis patients.
Wren
D R
DR
Department of Clinical Neurology, Institute of Neurology, Queen Square, London, United Kingdom.
Noble
M
M
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003165:Complement System Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D006358:Hot Temperature; D007700:Kinetics; D051379:Mice; D009103:Multiple Sclerosis / Q000473:pathology; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D009900:Optic Nerve / Q000166:cytology / Q000254:growth & development; D051381:Rats
D000911:Antibodies, Monoclonal; D003165:Complement System Proteins