Macrophage Fusion: The Making of a New Cell

Cell–cell fusion is a critical developmental step in most eukaryotes, as it is required for fertilization as well as for the formation of placenta, muscle and bone, where macrophages fuse to form a new cell called osteoclast. Macrophages can also fuse in chronic inflammatory reactions and in tumors where they form giant cells. While our understanding of the fusion mechanism used by viruses to infect cells has made major progress, the mechanism used by eukaryotic cells to fuse with one another remains poorly understood. Macrophages are unique in that they are mononucleate cells that fuse in rare instances to make a new cell, which suggests a regulated divergence from their routine activity. Here we discuss the formation of osteoclasts and giant cells with a special focus on the fusion mechanism of their mononucleate precursors, which belong to the mononuclear phagocyte lineage. We also discuss the unique mechanism macrophages utilize to recognize each other as self before they merge their cytoplasm into a new cell.