The role of cytokines and adhesion molecules in axon degeneration after peripheral nerve axotomy: a study in different knockout mice.
The loss of axons and axonal dysfunction has become of outstanding interest with respect to degenerative and inflammatory diseases of the central and peripheral nervous system. In particular in terms of demyelinating diseases such as multiple sclerosis it is important to know the mechanisms which are responsible for the degeneration and destruction of axons. Here we focused on the loss or preservation of axons after induction of Wallerian degeneration in transected mouse sciatic nerves. We examined the distal transected nerve segments of different knockout mice (ICAM-1; TNF-alpha; iNOS; IL-6) 6 days after axotomy. Despite a distinct number of invading macrophages which phagocytosed most of the myelin and axonal debris, we were able to demonstrate, that animals which are deficient for the cell adhesion molecule ICAM-1 and the cytokine TNF-alpha showed a significantly higher number of preserved axons within the degenerating distal nerve stump. Since macrophage invasion is known to be impaired in the absence of ICAM-1, these data indicate an essential role of these cells and their secreted factors, namely TNF-alpha, but not nitric oxide or IL-6 in the destruction of the axonal cytoskeleton in the peripheral nervous system.
Siebert
Heike
H
Institute of Neuropathology, Georg-August-Universität Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany.
Brück
Wolfgang
W
D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010525:Peripheral Nerves / Q000503:physiopathology*; D012584:Sciatic Nerve / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse