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Journal of Neuroscience, Vol 9, 2327-2335, Copyright © 1989 by Society for Neuroscience
Macrophage function during Wallerian degeneration of rat optic nerve: clearance of degenerating myelin and Ia expression
G Stoll, BD Trapp and JW Griffin
Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205.
This study examined Wallerian degeneration (WD) of rat optic nerve (ON)
with 2 goals: to determine which cell types are involved in myelin
degradation and clearance and to evaluate the extent to which Ia antigen, a
product of the immune response genes, is expressed. We examined
immunostained 1-micron and ultrathin cryosections of rat ON at 1, 8, and 16
weeks after nerve transection. Serial 1-micron cryosections were stained
with monoclonal antibodies to rat Ia antigen (Ox6) and with antibodies that
identify astrocytes (GFAP) and monocytes/macrophages (ED1). In normal ON,
ED1-positive cells were not found. A few ED1-positive monocytes/macrophages
were present in the transected ON at one week. Macrophages were prominent
throughout the ON at 8 weeks; by 16 weeks their number was decreasing.
These cells contained myelin debris in various stages of digestion.
GFAP-positive astrocytes did not contain myelin debris in their cytoplasm.
At all 3 times a subpopulation of the ED1-positive monocytes/macrophages
expressed Ia antigen. Ia antigen was not detected in endothelial cells or
GFAP-positive astrocytes. In ultrathin cryosections stained by immunogold
procedures, Ia immunoreactivity was found exclusively in cells containing
multiple vacuoles and myelin debris and lacking intermediate filaments. The
same cell type was labeled by ED1 antibodies. Our results indicate that
macrophages remove the vast majority of debris during Wallerian
degeneration in the CNS; a proportion of these macrophages concomitantly
express Ia antigen. These results suggest that the Ia expression by
macrophages observed in other CNS disorders does not necessarily reflect
specific local immune events, but in some instances can represent a
nonspecific response to CNS damage.
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