MFG-E8 Released by Apoptotic Endothelial Cells Triggers Anti-Inflammatory Macrophage Reprogramming

摘要: Apoptotic endothelial cells are an important component of the “response to injury” process. Several atherosclerosis risk factors such as hyperglycemia and oxidized low-density lipoproteins, immune injuries, antibodies complement, induce cell apoptosis. While apoptosis is known affect neighboring vascular wall biology, its consequences on macrophage reprogramming ill defined. In this study, we report that human mouse triggers release milk fat globule-epidermal growth factor 8 (MFG-E8) reprograms macrophages into anti-inflammatory cells. We demonstrated MFG-E8 released by apoptotic in a caspase-3-dependent manner. When were exposed conditioned media from serum-starved cells, they adopt high anti-inflammatory, low pro-inflammatory cytokine/chemokine secreting phenotype lost if absent media. Macrophage treatment with recombinant recapitulates effect Finally, showed MFG-E8-mediated occurs through increased phosphorylation signal transducer activator transcription-3 (STAT-3). Taken together, our study suggests key role demonstrates importance microenvironment responses.