Effects of radical oxygen species and antioxidants on macrophage polarization

Reactivc oxygen species (ROS) sccreted by inflammatory cells can lead to biomaterial implant degradation in the body, ultimately leading to implant failure. Macrophages, the dominant cell type recruited to implant sites, are known to secrete ROS and may be primarily responsible for oxidative damage. Macrophages initially play a pro- inflammatory role in wound healing (M1) and then polarize into pro-healing phenotypes to repair (M2a) and remodel (M2c) tissues. However, differences in secreted ROS between the macrophage phenotypes and their role in biomaterial degradation have not been well characterized. Antioxidants have been incorporated into implanted biomaterials to scavenge ROS, preventing oxidative degradation of the biomaterial. The depletion of extracellular ROS in the local environment may have off-target effects on macrophage behavior. Here we show that M1 and M2c macrophages produce significantly higher quantities of intracellular ROS compared to M0 and M2a macrophages. In a preliminary study of the direct effects of ROS on macrophage behavior. M1 macrophages treated with 10uM H2O2 for 12-hours exhibited a slight upregulation of M2 markers. Interestingly, H2O2 did not affect M0 macrophage gene expression. These data suggest that ROS may play a role in M2 macrophage polarization, and antioxidants may therefore inhibit this activity of macrophages.