Neuregulin and erbB receptor expression in normal and diseased human whitematter

Human white matter from non-neurologic cases, multiple sclerosis (MS) and o ther neurologic diseases (OND, inflammatory and non-inflammatory), was subj ected to immunocytochemistry and Western blotting for expression of the neu regulin, glial growth factor-2 (GGF2), and its receptors, erbB2, erbB3 and erbB4. GGF2 has previously been shown to have mitogenic effects upon oligod endrocytes in vitro and an enhancing effect upon remyelination in animals w ith autoimmune demyelination. In all types of human white matter examined, expression of the ligand GGF2 and its three receptors was consistently foun d on oligodendrocytes, with higher levels being seen in cases of MS. Expres sion was also seen, albeit at lower levels, on astrocytes and microglial ce lls, the latter most commonly in MS and OND. In human lymph node tissue, so me lymphocytes were positive for erbB2, erbB3 and erbB4. Western blots conf irmed the presence of all three receptors in normal, MS and OND white matte r. GGF2 and erbB receptor expression did not correlate with areas of remyel ination and reactivity occurred throughout the tissue, with some increase i n intensity at the edge of MS lesions. Examination of precursor oligodendro cyte immunoreactivity (with anti-PDGF-R alpha and NG2), revealed widespread expression throughout both normal and diseased white matter. The presence of GGF2 and its receptors on oligodendrocytes and lymphocytes render this c ell type a candidate for functional signaling via this pathway, perhaps in relationship to myelinating activity. (C) 1999 Elsevier Science B.V. All ri ghts reserved.