Metabolic Immunomodulation, Transcriptional Regulation, and Signal Protein Expression Define the Metabotype and Effector Functions of Five Polarized Macrophage Phenotypes

Furthermore, both M2c and M2d macrophages activate angiogenesis processes, but M2c macrophages promote extracellular matrix (ECM) assembly while M2d macrophages activate processes that drive ECM degradation. Finally, metabolomics profiles further validate recent findings that shifts between aerobic glycolysis, the pentose phosphate pathway, and oxidative phosphorylation distinguish pro-inflammatory macrophages and tissue repair/regeneration macrophages; however, our model provides further evidence to support the association between metabolism (such as decoupling of the TCA cycle, fatty acid synthesis, and -oxidation) and functional phenotype. Metabolomics is fundamentally changing our understanding of immunomodulation in diverse macrophage populations and that deeper understanding is informing our long-term goals of developing novel diagnostic and therapeutic approaches to wound healing. By integrating metabolomics into our systematic characterization of these phenotypes, we have developed quantifiable metrics that not only define metabolic and functional phenotype, but also provide insight into the cellular functions fundamental to macrophage plasticity. Summary Sentence