Enhanced expression of NGF receptors in multiple sclerosis lesions

The receptor for nerve growth factor (NGF) comprises a 75-kDa (NGFR(p75)) 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 NGFR(p75). Only the 2 mAbs specifically recognized NGFR(p75), while the polyclonal antiserum showed widespread reactivity. In normal CNS and silent MS lesions, immunohistochemistry with anti-NGFR(p75) mAbs and for TrkA revealed perivascular cell reactivity. At the edge of chronic active MS lesions, selective NGFR(p75) staining was prominent on reactive astrocytes, while throughout the lesion, NGFR(p75) was expressed on microglia/macrophages. The vast majority of mature or precursor oligodendrocytes did not express NGFR(p75). Both NGF receptors were co-expressed on a subset of inflammatory cells. Immunoreactivity for NGFR(p75) 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.