The role of Schwann cells and macrophages in the removal of myelin during Wallerian degeneration.

Abstract

Axonal changes, in particular the breakdown and removal of the myelin sheath, were studied using morphological method and cytochemical technique in the sciatic nerves of rats following transection. The details of axonal loss were examined during the first few days after transection. Axonal degradation was immediately accompanied by the fragmentation of the myelin sheath. It was found that: (a) a part of the myelin sheath separated from Schwann cells and smashed into debris, then the myelin debris was phagocytosed and digested by macrophages at endoneurial space; the others, most of the myelin sheath, remained within Schwann cells until being digested; (b) both small debris of myelin sheath (SDMS) and large membrane-bound myelin debris (LMBMD) were found in Schwann cells; acid phosphatase (AcPase) activity was detected in SDMS earlier than in LMBMD; (c) macrophages were found in myelin sheath tubes; they participated in removing a part of degenerating axons. Observation confirmed that Schwann cells had no ability to actively phagocytose myelin, that the majority of myelin debris were removed by Schwann cells, and that the minority of them were dealt with by macrophages. The ability of Schwann cells to digest myelin debris suggested that Schwann cells play a crucial role in vivo in removing myelin debris and that the process of myelin debris in Schwann cells might be significant for their mitotic activity.

Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss

“…Additionally, our data do not support cell death via an anaphylatoxin signaling mechanism because although C3aR is expressed by neurons 54 , 61 , 62 , C3a was not toxic at the concentrations tested, and importantly, C3a actually increased neurite outgrowth in vitro. A role for direct phagocytosis cannot be completely excluded, as both astrocytes and Schwann cells have been demonstrated to possess phagocytic capacity 63 – 67 , and are likely to be present in our DRG cultures based on the presence of p75+/βTubulinIII- and S100+/βTubulinIII- immunolabeled cells (data not shown), as well as previous reports 66 . Finally, rather than promote direct toxicity, it is possible that C3/C3b instead causes deficits in cell adhesion, either by direct interference or indirectly following receptor mediated signal cascade activation.…”

Neuromatous Regeneration as a Nerve Response After Catheter-Based Renal Denervation Therapy in a Large Animal Model

“…33 In humans, the time between nerve injury and detectable axon degeneration is several days. 34 SCs respond to axonal injury by phagocytizing and presenting debris to macrophages 35,36 and by rapid proliferation 37,38 as early as 3 days after injury. 37 At the same time, SC and macrophages are stimulated by cytokines (macrophage-derived interleukin 1) to produce nerve growth factor.…”

Myelin phagocytosis by macrophages and nonmacrophages during Wallerian degeneration

“…2) It is phagocytosed by macrophages that have migrated into the vacuoles of SCs (Fig.2B) (Hirata et al, 1999). 3) It is digested in the vacuoles of the cytoplasm in SCs by utilizing hydrolytic enzymes through fusion with lysosomes (Han et al, 1989;Hirata et al, 1999;Holtzman and Novikoff, 1965). Thus, the myelin removal starts with the segmentation of their own membrane of SCs, i.e., myelin and is followed by incorporation of the segmented myelin into SCs.…”