Phospholipase A2 plays an important role in myelin breakdown and phagocytosis during wallerian degeneration

Abstract

Phospholipase A2 (PLA2) hydrolyzes phosphatidylcholine to lysophosphatidylcholine and arachidonic acid. The former can induce myelin breakdown and the latter, via eicosanoids, can stimulate inflammatory responses. Immunohistochemical analysis of secreted (sPLA2) and cytosolic (cPLA2) forms of the enzyme was assessed in the injured adult rat sciatic and optic nerves. sPLA2 and cPLA2 are expressed in the first 2 weeks in the injured sciatic nerve, which correlates with rapid Wallerian degeneration in peripheral nerves. In contrast, both forms of PLA2 were not expressed in the optic nerve for the first 3 weeks after crush injury, which correlates with slow Wallerian degeneration in the central nervous system (CNS). In addition, PLA2 is not expressed in the lesioned sciatic nerve of C57BL/Wlds mutant mice in which Wallerian degeneration is severely retarded. Blocking cPLA2 in the transected sciatic nerve of C57BL/6 mice, which have a naturally occurring null mutation for the major from of sPLA2, resulted in a marked slowing of myelin and axonal degradation and phagocytosis in the distal nerve segment. These results provide direct evidence of an important role for cPLA2 in Wallerian degeneration.