MOLECULAR-BIOLOGY OF MICROGLIA CYTOKINE AND CHEMOKINE RECEPTORS AND MICROGLIAL ACTIVATION

Activation of brain microglial cells can be subdivided into a number o f stages. Early stages likely are proliferation and migration to sites of cell damage. These two stages have been studied exemplarily on the IL-3 receptor beta-subunit and on the CC-chemokine receptor 5 using m olecular biological methods. First, IL-3 receptor beta-subunit cDNA ha s been cloned in full length from rat microglia. Since cultured microg lia are already activated to some extent, mRNA of this subunit has bee n detected in the isolated cells, but was absent in normal rat brain. Lipopolysaccharide (LPS) increased this mRNA in the cultured cells and LPS injected into the circulation of rats induced the mRNA specifical ly in brain microglia as revealed by in situ hybridizations. Next, we obtained partial cDNAs of receptor-coupled protein tyrosine kinases JA K 1 and JAK 2. These mRNAs were present both in cultured microglia and in rat brain, but were not influenced by LPS. Finally, a full-length cDNA of the rat chemokine receptor 5 has been obtained by PCR methodol ogy. Its mRNA was increased by administration of LPS both in cultured microglia and in vivo. It is expected, that further investigations on these receptors could help to develop improved strategies to combat ch ronic inflammatory events in the brain.