title: Enhanced expression of NGF receptors in multiple sclerosis lesions.
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.
authors.affiliation: Clinica Neurologica, Ospedale Policlinico, Azienda Ospedaliera of Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Valdo
authors.forename: Chiara
authors.initials: C
authors.lastname: Stegagno
authors.forename: Sara
authors.initials: S
authors.lastname: Mazzucco
authors.forename: Elisa
authors.initials: E
authors.lastname: Zuliani
authors.forename: GianLuigi
authors.initials: G
authors.lastname: Zanusso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Moretto
authors.forename: Cedric S
authors.initials: CS
authors.lastname: Raine
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonetti
mesh_terms: D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D017475:Receptors, Nerve Growth Factor; D020917:Receptor, trkA