The role of nucleotides in apoptotic cell clearance: implications for disease pathogenesis

Apoptosis occurs in many tissues, during both normal and pathogenic processes. Normally, apoptotic cells are rapidly cleared, either by neighboring or recruited phagocytes. The prompt clearance of apoptotic cells requires that the apoptotic cells announce their presence through the release of chemotactic factors, known as “find-me” signals, to recruit phagocytes to the site of death, and through the exposure of so-called “eat-me” signals, which are ligands for phagocytic uptake. The importance of prompt apoptotic cell clearance is revealed by findings that decreasing the efficiency of engulfment results in the persistence of apoptotic cells, which is often associated with chronic inflammation and autoimmunity. Additionally, the proper clearance of apoptotic cells is actively anti-inflammatory, which is thought to play a crucial role in immunologic tolerance. Therefore, defects associated with clearance of apoptotic cells may contribute to the pathogenesis of several inflammatory diseases, including autoimmunity and atherosclerosis. Here, we review the role of nucleotides in the apoptotic cell clearance process and discuss their implications for disease pathogenesis.