Effects of the immunomodulator linomide on macrophage migration and myelin phagocytic activity in peripheral nerve trauma: an experimental study.
Wallerian degeneration after peripheral nerve transection leads to the phagocytosis of degenerated myelin and axon components by macrophages. These phagocytes are recruited from the systemic circulation and Wallerian degeneration may therefore be used as a model for myelin removal by hematogenous macrophages, a feature that is also a hallmark of demyelinating diseases of the central and peripheral nervous system. The immunomodulator linomide has been shown to be effective in the treatment of experimental demyelinating diseases although the exact mode of its action is not yet defined. The present study investigated the effect of linomide on monocyte invasion and myelin phagocytosis after sciatic nerve transection. Linomide had a dual effect in Wallerian degeneration. Monocyte migration from the circulation to the damaged nervous system was significantly reduced. Additionally, the myelin phagocytic capacity of macrophages was impaired, finally resulting in a significant delay in the removal of myelin. The present experiments may provide an explanation for the effects of linomide during the course of demyelinating diseases of the nervous system.
Vougioukas
V I
VI
Department of Neuropathology, Charité, Berlin, Germany.
Siebert
H
H
Heinecke
K
K
Brück
W
W
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002464:Cell Migration Inhibition; D006912:Hydroxyquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000276:immunology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D012584:Sciatic Nerve / Q000187:drug effects / Q000276:immunology / Q000293:injuries; D014855:Wallerian Degeneration / Q000276:immunology
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; C045282:roquinimex