Kurt Williams, Brigham Young University
Life Sciences
Macrophages play an important role in innate and adaptive immune responses, inflammation, and tissue repair and are characterized by two distinct phenotypes: classically-activated (M1) and alternatively-activated (M2) macrophages. M1 macrophages are characterized by a pro-inflammatory phenotype and are involved in production of pro-inflammatory cytokines and aggressive engulfment, whereas M2 macrophages are characterized by an anti-inflammatory phenotype and are involved in production of anti-inflammatory cytokines (e.g. IL-10) and tissue repair. Macrophage engulfment of apoptotic cells leads to polarization toward the M2 phenotype and is thus “immunologically silent”. Additionally, there is evidence that tumor-associated macrophages (TAMs) tend toward an M2 phenotype and as a result offer protection from an immune response in the tumor microenvironment. To further investigate the role of necrotic and apoptotic cells in regulating macrophage polarization, we cultured human macrophages with necrotic, apoptotic, or standard viable Raji cells and fluorescent beads and performed an engulfment assay. In a preliminary study we found that macrophages cultured with apoptotic cells showed a decrease in engulfment levels compared to macrophages cultured with necrotic cells. Macrophages cultured with standard viable Raji cells had the lowest levels of engulfment compared to macrophages cultured with apoptotic cells or necrotic cells. Thus, in our initial experiments macrophages cultured with necrotic cells appear to have a more “M1” phenotype, whereas macrophages cultured with apoptotic cells appear to have a more “M2” phenotype. Further experiments are necessary to validate this preliminary data and further characterize the capabilities of necrotic and apoptotic cells to differentially polarize macrophages. If these observations are replicated, it has potential applications in cancer biology and therapeutics, atherosclerosis, diabetes, autoimmunity, and other diseases with an inflammatory component.