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Differential expression of fibroblast growth factor‐2 and receptor by glial cells in experimental autoimmune encephalomyelitis (EAE)
Author(s) -
Gehrmann Jochen,
LannesVieira Joseli,
Wekerle Hartmut
Publication year - 1996
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199602)16:2<93::aid-glia1>3.0.co;2-b
Subject(s) - microglia , biology , experimental autoimmune encephalomyelitis , basic fibroblast growth factor , fibroblast growth factor , immunocytochemistry , t cell , immunology , in situ hybridization , receptor , inflammation , microbiology and biotechnology , pathology , growth factor , endocrinology , immune system , gene expression , medicine , biochemistry , gene
To assess the expression pattern of basic fibroblast growth factor (FGF‐2) and one of its receptors (FGFR‐1/flg) during autoimmune inflammation of the CNS, FGF‐2, and FGFR1/flg peptide and mRNA levels were examined by immunocytochemistry, by in situ hybridisation and by Northern blot analysis in T cell‐mediated EAE of the Lewis rat. In naive control animals as well as in animals injected with nonencephalitogenic, PPD‐reactive T lymphocytes, FGF‐2 immunoreactivity was low and confined to blood vessels and to a few spinal cord neurons. In rats injected with encephalitogenic, MBP‐reactive T lymphocytes, however, FGF‐2‐immunoreactive cells were detected from day 4 after T cell transfer onward, i.e., from the onset of clinical symptoms. The number of FGF‐2 immunoreactive cells was highest between days 6 and 10 after T cell transfer. Increased FGF‐2 peptide expression was paralleled by increased FGF‐2 mRNA expression on macrophages/microglia in the spinal cord. By 21 days after T cell transfer, i.e. after complete recovery, FGF‐2 peptide and mRNA expression had fully subsided. Based on morphological criteria and on double labeling with the macrophage/microglia‐binding lectin GSI‐B 4 two cell types expressed FGF‐2: 1) round macrophages within the core, and 2) activated microglia at the edges of white and grey matter perivascular lesions. Paralleling the temporal and spatial expression pattern of FGF‐2, FGFR‐1/flg immunoreactivity was induced on activated macrophages/microglia but also on reactive astrocytes bordering perivascular inflammatory lesions. In situ hybridisation analysis furthermore showed that macrophages/microglia expressed the FGFR‐1/flg mRNA, and that receptor mRNA expression paralleled ligand mRNA expression. Macrophage/microglia‐derived FGF‐2 could serve two main functions in EAE: 1) regulate microglial activation in an autocrine fashion, and 2) help to target astrocyte‐derived insulin‐like growth factor‐I (IGF‐I) to potentially injured oligodendrocytes in demyelination. © 1996 Wiley‐Liss, Inc.