DIFFERENTIAL EXPRESSION OF FIBROBLAST GROWTH FACTOR-II AND RECEPTOR BY GLIAL-CELLS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE)

To assess the expression pattern of basic fibroblast growth factor (FG F-2) and one of its receptors (FGFR-1/flg) during autoimmune inflammat ion of the CNS, FGF-2, and FGFR1/flg peptide and mRNA levels were exam ined by immunocytochemistry, by in situ hybridisation and by Northern blot analysis in T cell-mediated EAE of the Lewis rat. In naive contro l animals as well as in animals injected with nonencephalitogenic, PPD -reactive T lymphocytes, FGF-2 immunoreactivity was low and confined t o blood vessels and to a few spinal cord neurons. In rats injected wit h encephalitogenic, MBP-reactive T lymphocytes, however, FGF-a-immunor eactive cells were detected from day 4 after T cell transfer onward, i .e., from the onset of clinical symptoms. The number of FGF-2 immunore active cells was highest between days 6 and 10 after T cell transfer. Increased FGF-2 peptide expression was paralleled by increased FGF-2 m RNA expression on macrophages/microglia in the spinal cord. By 21 days after T cell transfer, i.e. after complete recovery, FGF-2 peptide an d mRNA expression had fully subsided. Based on morphological criteria and on double labeling with the macrophage/microglia-binding lectin GS I-B-4 two cell types expressed FGF-8: 1) round macrophages within the core, and 2) activated microglia at the edges ofwhite and grey matter perivascular lesions. Paralleling the temporal and spatial expression pattern of FGF-8, FGFR1/flg immunoreactivity was induced on activated macrophages/microglia but also on reactive astrocytes bordering periva scular inflammatory lesions. In situ hybridisation analysis furthermor e showed that macrophages/microglia expressed the FGFR-1/flg mRNA, and that receptor mRNA expression paralleled ligand mRNA expression. Macr ophage/microglia-derived FGF-8 could serve two main functions in BAE: 1) regulate microglial activation in an autocrine fashion, and 2) help to target astrocyte-derived insulin-like growth factor-I (IGF-I) to p otentially injured oligodendrocytes in demyelination. (C) 1996 Wiley-L iss, Inc.