Journal of Neuropathology and Experimental
Neurology: Vol. 61, No. 1, pp. 91–98.
Paola Valdo, PhD, Chiara Stegagno,
MD, Sara Mazzucco, MD, Elisa Zuliani, GianLuigi Zanusso, MD, PhD, Giuseppe
Moretto, MD, Cedric S. Raine, PhD, DSc, FRCPath, and Bruno Bonetti, MD,
PhD
Abstract
The receptor for nerve growth factor
(NGF) comprises a 75-kDa (NGFRp75) and a tyrosine kinase A (TrkA) subunit.
In view of conflicting opinions on
the identity of glial targets of NGF in human central nervous system (CNS),
we examined the cellular distribution of both NGF receptor subunits in
normal CNS and in chronic multiple sclerosis (MS) lesions.
For this, we compared the pattern
of recognition of 2 monoclonal antibodies (mAbs) and a polyclonal antiserum
to NGFRp75.
Only the 2 mAbs specifically recognized
NGFRp75, while the polyclonal antiserum showed widespread reactivity.
In normal CNS and silent MS lesions,
immunohistochemistry with anti-NGFRp75 mAbs and for TrkA revealed perivascular
cell reactivity.
At the edge of chronic active MS
lesions, selective NGFRp75 staining was prominent on reactive astrocytes,
while throughout the lesion, NGFRp75 was expressed on microglia/macrophages.
The vast majority of mature or precursor
oligodendrocytes did not express NGFRp75.
Both NGF receptors were co-expressed
on a subset of inflammatory cells.
Immunoreactivity for NGFRp75 on glial
and immune cells did not correlate with the distribution of apoptotic figures,
as detected by TUNEL.
Thus, expression of NGF receptors
in active MS lesions suggests a role for NGF in regulating the autoimmune
response at both immune and glial cell levels.
© Copyright by American Association
of Neuropathologists, Inc. 2002