Brain Activation of Monocyte Lineage Cells: Brain-Derived Soluble Factors Differentially Regulate BV2 Microglia and Peripheral Macrophage Immune Functions

Brain injury and subsequent neurodegeneration are often associated with infiltrating leukocytes and the activation of microglia as well as other infiltrating cells. However, the characteristics of activation are poorly understood. The objective of this study was to further the understanding of brain regulation of microglial activation. We used an organotypic coculture paradigm to assess how brain-derived soluble factors modulate microglia and peripheral macrophage activation through microscopy and flow cytometry techniques. In the presence of brain-derived soluble factors, the BV2 microglia cell line increased MHC II and phagocytic receptor (Fcγ II/III) expression. The increased expression correlated with a functional increase in phagocytic activity, but did not correlate with an increase in allostimulation ability. Furthermore, this interaction was selective to an interaction between brain-derived soluble factor(s) and BV2 microglia, since it was not observed in the ANA1 macrophage cell line or in primary peritoneal macrophages. The results indicated that brain-derived soluble factor(s) modulate microglial activation in a manner that is distinct from the effects on peripheral macrophages. Moreover, our results suggest that inflammatory events associated with some types of brain injury may be induced by the brain without dependence on infiltrating peripheral macrophages or T lymphocytes.