SCHWANN-CELLS DEGRADE MYELIN AND PROLIFERATE IN THE ABSENCE OF MACROPHAGES - EVIDENCE FROM IN-VITRO STUDIES OF WALLERIAN DEGENERATION

Interruption of axonal continuity in peripheral nerve trunks leads to axonal and myelin breakdown and removal distal to the injury site, a p rocess known as Wallerian degeneration. Clearance of axonal and myelin debris has been attributed to the cooperative actions of two cell typ es, the indigenous Schwann cells and macrophages recruited to the regi ons of tissue damage. Recent work in this area has suggested a limited role for Schwann cells in myelin degradation and has emphasized the r ole of macrophages, not only in myelin clearance but also in the stimu lation of Schwann cell proliferation which also occurs during Walleria n degeneration. In this report, we demonstrate that rat Schwann cells are capable of substantial myelin degradation unaided by macrophages. Observations were made following excision of neuronal somata from well -myelinated rat dorsal root ganglion newon/Schwann cell co-cultures. T he various stages of myelin breakdown were observed by phase microscop y, Sudan black staining or electron microscopy. The time course for br eakdown of individual myelin internodes varied from 2 to 10 days after injury and was to some extent dependent upon the original intemodal l ength. Additionally, we show that most Schwann cells involved in Walle rian degeneration in the absence of macrophages undergo cell division following degradation of myelin into granules visible by light microsc opy. The co-cultures employed were essentially free of macrophages as assessed by immunostaining for the OX42, ED2, and ED1 macrophage marke rs. No macrophages were detected by light or electron microscopy in th e vicinity of the identified Schwann cells and furthermore, macrophage s/monocytes were rarely observed in uninjured co-cultures as assessed by fluorochrome-conjugated acetylated LDL labelling. These results pro vide evidence in support of the ability of Schwann cells to carry out degradation of short myelin segments and to proliferate without macrop hage assistance during Wallerian degeneration in vitro.