Clearance of apoptotic cells: Implications in health and disease

Center for Cell Clearance and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 06/2010; 189(7):1059-70. DOI: 10.1083/jcb.201004096
Source: PubMed


Recent advances in defining the molecular signaling pathways that regulate the phagocytosis of apoptotic cells have improved our understanding of this complex and evolutionarily conserved process. Studies in mice and humans suggest that the prompt removal of dying cells is crucial for immune tolerance and tissue homeostasis. Failed or defective clearance has emerged as an important contributing factor to a range of disease processes. This review addresses how specific molecular alterations of engulfment pathways are linked to pathogenic states. A better understanding of the apoptotic cell clearance process in healthy and diseased states could offer new therapeutic strategies.

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    • "If not successfully taken up by phagocytes, apoptotic cells proceed to the phase of late apoptosis when the plasma membrane becomes permeable for macromolecules [25]. The leakage of intracellular molecules during secondary necrosis provokes an inflammatory response [8], but the pre-treatment with LO-3 probably delay secondary necrosis triggered by the treatment with the nephrotoxic drugs and consequently inhibit the pro-inflammatory response. Associated with cell death/apoptosis, autophagy is a constitutive cellular event and is enhanced under certain conditions such drug treatments [14]. "
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    • "Mobilized monocyte-derived macrophages extravasate to inflammatory tissue sites and clear apoptotic PMN in a nonphlogistic fashion by the process of efferocytosis . Apoptotic PMN release " find-me " signals that are sensed by extravasated macrophages [3]. Following phagocytosis, apoptotic PMN provides resolution cues to macrophages by evoking distinct signaling events that block release of proinflammatory mediators thus allowing further engulfment of apoptotic cells. "
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    • "Increasing evidence suggest that improper clearance of apoptotic cells, being the result of either genetic anomalies and/or a persistent disease state, contributes to the establishment and progression of a number of human diseases via affects on the maintenance of tissue homeostasis, tissue repair, and inflammation (6). Autoimmune disorders, in which both animal models and human research indicate a strong relationship between improper clearance and the development of the disease, represent the best characterized example of such diseases. "
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