IDENTIFICATION OF MACROPHAGE-MIGRATION INHIBITORY FACTOR MESSENGER-RNA EXPRESSION IN NEURAL CELLS OF THE RAT-BRAIN BY IN-SITU HYBRIDIZATION

Macrophage migration inhibitory factor (MIF) has been rediscovered as a hormone and immunomodulator as well as a proinflammatory cytokine. W e investigated the expression of MIF protein and mRNA in the rat brain using optimized immunohistochemistry and in situ hybridization, respe ctively. By immunohistochemical analysis, we found that MIF protein wa s present in the epithelial cells of the choroid plexus and ependymal cells as well as astrocyte-like cells in the cerebral white matter and cortex. Tissue sections double-stained for glial fibrillary acidic pr otein (GFAP) and MIF revealed the presence of MIF protein in astrocyte s, whereas this protein was scarcely identified in the neurons by stai ning using an anti-MIF antibody. We also measured the MIF content in t he cerebrospinal fluid, which was 15.5 +/- 2.5 ng/ml (mean +/- SEM), c omparable to the serum MIF value. In contrast, expression of MIF mRNA was found not only in astrocytes but also in neurons by the in situ hy bridization technique. These results suggest that MIF plays a pivotal role as an immunomodulatory cytokine for inflammatory reactions and im mune responses in the whole central nervous system. (C) 1998 Elsevier Science Ireland Ltd.