Macrophages: their myelinotrophic or neurotoxic actions depend upon tissue oxidative stress.

There are still questions regarding whether macrophages found in MS lesions are agents of recovery or of destruction. To address this, we examined in aggregate cultures prepared from dissociated embryonic spinal cord tissue, with or without addition of exogenous macrophages, the effect of menadione-induced oxidative stress. Similar to findings of other laboratories, we observed that in the absence of oxidative stress macrophage enrichment promoted myelinogenesis. In macrophage-poor cultures, menadione at 5 microM had very little effect upon the status of the aggregate cultures; however, increasing this to 10 and 20 microM did result in some damage to axons and myelin. By contrast, in macrophage enriched cultures, menadione at a concentration as little as 5 microM caused the complete destruction of the aggregates. We suggest that in neural tissues that have sufficiently high macrophage numbers, oxidative stress results in a positive inflammatory feedback loop that results in massive tissue destruction. We further suggest that what we see in macrophage-enriched aggregates subjected to oxidative stress may represent what happens in the Marburg-type of MS lesion.