Differentiated Expression Patterns and Phagocytic Activities of Type 1 and 2 Microglia.

Abstract

The purpose of this study was to elucidate the differentiated expression patterns and phagocytic activities of two subtypes of microglia. A rat optic nerve crush model was used to identify the expression patterns of two subtypes of microglia. Primary microglia were isolated from rat mixed glial cultures. Subsequently, in vitro experiments evaluating the phagocytosis of axonal debris were performed to analyze responsiveness to immunologic modulators (lipopolysaccharide [LPS], interleukin [IL]-4 and interferon [IFN]-γ), and we assessed the effects of LPS and IL-4 in the optic nerve crush model. The expression levels of IL-4-associated signaling molecules were analyzed in immunoblotting experiments. In the optic nerve crush model, increased numbers of microglia were found, and a minor and transient population was identified as type 1 microglia. The type 2 microglia phagocytosed more axonal debris than the type 1 microglia. The activities of both subtypes of microglia were enhanced by treatment with LPS and IFN-γ. However, the phagocytic activity of the type 1 microglia, which showed activated STAT6 signal transduction, was significantly inhibited by stimulation with the anti-inflammatory cytokine IL-4. LPS reduced the fragmentation of axons in crushed nerve fibers, whereas the axonal debris remained in IL-4-treated rats subjected to optic nerve crush. The present study revealed the time-dependent distribution of the two subpopulations of microglia in an optic nerve crush model and IL-4-dependent inhibition of the phagocytosis of axonal debris by type 1 but not type 2 microglia.