Extracellular cardiolipin regulates select immune functions of microglia and microglia-like cells.

Cardiolipin is a mitochondrial membrane phospholipid with several well-defined metabolic roles. Cardiolipin can be released extracellularly by damaged cells and has been shown to affect peripheral immune functions. We hypothesized that extracellular cardiolipin can also regulate functions of microglia, the resident immune cells of the central nervous system (CNS). We demonstrate that extracellular cardiolipin increases microglial phagocytosis and neurotrophic factor expression, as well as decreases the release of inflammatory mediators and cytotoxins by activated microglia-like cells. These results identify extracellular cardiolipin as a potential CNS intercellular signaling molecule that can regulate key microglial immune functions associated with neurodegenerative diseases.