TNF-alpha suppresses CR3-mediated myelin removal by macrophages.
Mononuclear cells of the monocyte/macrophage system play an important role in myelin ingestion during Wallerian degeneration. The present in vitro study clarifies the role in this process of two macrophage-secreted cytokines, TNF-alpha and interleukin-1. Treatment with TNF-alpha massively reduced the amount of myelin ingested by macrophages via their complement receptor type 3 (CR3). Anti-TNF-alpha antibodies reversed the effect. Immunofluorescence of macrophages indicated that TNF-alpha caused a reduced expression of the CR3 by phagocytic cells. Further experiments revealed an interaction of TNF-alpha with its receptor on the macrophage cell membrane. Interleukin-1 had no effect on myelin ingestion in the in vitro system used in these experiments.
Department of Neuropathology, University of Göttingen, Germany.
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Brück
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Friede
D000818:Animals; D003584:Cytological Techniques; D005455:Fluorescent Antibody Technique; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009410:Nerve Degeneration; D010587:Phagocytosis; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D012460:Sulfasalazine / Q000494:pharmacology; D013864:Thioglycolates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016177:Macrophage-1 Antigen; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; C017487:2-mercaptoacetate