**4. Conclusions**

Macrophages, derived from either bone marrow monocytes or embryonic stem cells have crucial functions during immune response and homeostasis. Stem cell derived tissue specific macrophages are metabolically and functionally specialized to enable them play their role within specific tissues. In terms of immune response, macrophages are highly dynamic largely due to influence of low weight molecules such as intermediate metabolites within the tissue matrix. In turn, metabolic process occurring within macrophages and by extend extracellularly tend to modify the functioning of activated macrophages. As described, classically activated macrophages perform much of glycolysis and fatty acid synthesis to rapidly produce energy and remodel cell membrane. They also have breakpoints in the TCA cycle which allows intermediate products to accumulate and activate proinflammatory pathways. Contrary, alternatively activated macrophages predominantly utilize oxidative phosphorylation reactions and fatty acid oxidation to fuel their cellular activities and have an intact TCA cycle. However, to be noted, is that both M1 and M2 macrophages have been shown to depict a mixed metabolic picture. Additionally, the complexity of how metabolic processes are woven within cells makes it difficult to pin point a single pathway as either specialized in M1 or M2 macrophages. As such, we cannot conclusively state that above metabolic processes are delineated to specific macrophage polarization; rather it suggests that some metabolic pathways predominate either during inflammatory or anti-inflammatory events.
