Complement-dependent phagocytosis in the clearance of various cellular targets.

Abstract

Phagocytosis is the process of recognition and uptake of cells or large cellular debris; this process contributes to the removal of pathogens, cancerous cells and dead cells from the human body. Phagocytosis is greatly enhanced by the deposition of opsonins on the target cells, which act as a bridge between the target cell and the phagocyte. The two most studied types of opsonins are antibodies and complement proteins. Despite extensive research into the mechanisms of phagocytosis, it is still not entirely understood to what extent antibodies and complement contribute individually to the clearance of cellular targets. In this review, we provide an overview of the complement system and outline its relative role in the clearance of apoptotic cells, pathogens, cancer, myelin and synapses in the central nervous system. We discuss the contribution of complement to phagocytosis in both homeostasis and pathology, and describe complement-based therapeutic strategies to regulate phagocytosis under various pathological conditions. We conclude that complement is necessary for the optimal clearance of apoptotic cells, pathogens, myelin, cellular debris and weak synapses. Except in the case of synapses, there is still ongoing debate as to whether complement optimally induces phagocytosis in the absence of antibodies. In case of cancer cells, it is currently unclear whether complement plays a substantial role in phagocytosis and elimination. Knowing the exact role of complement in phagocytosis allows us to better understand the pathogenesis of multiple diseases and develop better therapies to treat them.