Proteomic signature of environmental oxygen tension modulation of human macrophage polarization and functions

Macrophages are innate immune cells characterized by their plasticity and their ability to react to various environmental stimuli. These cells are involved in a multiple number of tissular functions in homeostasis and pathological contexts. According to their environment these cells could be polarized toward different states of activation which determine their functional orientation. A large part of the macrophage biology field is devoted to better define what polarizations are, from a molecular point of view. It is now accepted that a multidimensional model of polarization is needed to grasp the broad phenotype repertoire depending on various environmental signals. Oxygen tension is one of these tissular environmental parameters. We designed this study to obtain a proteomic signature of various polarizations in human monocytes derived macrophages. We also seek to explore how environmental oxygen tension varying from an atmospheric composition (18.6% O2) to a “tissular normoxia” (3% O2) could modify our classification of macrophages’ polarization. We have obtained various polarization specific proteins and oxygen sensors for human macrophages. One example is arachidonate 15-lipoxygenase (ALOX15) which is a IL4/IL13 polarization specific proteins up regulated under low oxygen exposure associated to an increase of the phagocytosis rate of apoptotic cells. These results illustrate the necessity to take into account physicochemical parameters like oxygen when macrophage polarization is studied to correctly assess their functions in tissues.