Effects of differently activated rodent macrophages on sensory neurons: implications for XXXX .

@entity4655 @entity625 @entity39 @entity5 @entity12718 @entity1505 @entity842 @entity158 @entity35 @entity528 @entity13624
OBJECTIVE: In @entity625 , macrophages invade the affected joint. Experimental @entity625 models have shown that macrophages also invade the dorsal root ganglia (DRGs) of the inflamed segments in which the perikarya of sensory neurons are located. It is unclear whether this macrophage invasion contributes to @entity158 and/or furthers @entity528 . The present study was undertaken to investigate how differently activated macrophages affect DRG neurons. METHODS: We determined the phenotype of macrophages in the DRGs of rats with @entity625 ( @entity625 ). In a DRG neuron-macrophage coculture system, we investigated whether differently activated macrophages (stimulated with either lipopolysaccharide [LPS]/interferon-y [IFNy], @entity5 @entity39 factor [ @entity1505 ], or @entity12718 ) damage DRG neurons and/or stimulate them to release the mediator @entity4655 ( @entity4655 ), which promotes @entity158 and @entity13624 . RESULTS: Macrophages in the DRGs of @entity35 with @entity625 showed the phenotype of @entity1505 -stimulated macrophages but did not express inducible @entity842 synthase, which was found in cultured macrophages only after LPS/IFNy activation. In neuron-macrophage cocultures, activation of macrophages stimulated DRG neurons to release @entity4655 within 1 hour, indicating neuronal activation by macrophages. Only 48-hour activation of macrophages with LPS/IFNy increased the neuronal cell death rate in culture, provided that the macrophages were in direct contact with DRG neurons. This effect was dependent on @entity842 . CONCLUSION: Macrophages have the potential to stimulate sensory neurons in the DRGs, and this may contribute to @entity158 . If they are classically activated, such as after LPS/IFNy stimulation, this may also further neuronal cell death. This is not the case in @entity625 but may occur in models involving @entity528 .
