Article

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

ABSTRACT

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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Available from: Kodi Ravichandran
    • "Apoptotic cells are barely seen unengulfed by phagocytes in normal tissues, indicating that their removal occurs concurrently with progression of apoptosis (Franc, 2002;Gregory & Devitt, 2004;Henson & Hume, 2006;Lauber, Blumenthal, Waibel, & Wesselborg, 2004). Defects in the clearance of apoptotic cells may lead to inflammation, autoimmune responses, and developmental abnormalities (Elliott & Ravichandran, 2010;Hanayama & Nagata, 2005;Hanayama et al., 2004;Juncadella et al., 2013;Lu et al., 2011;Mahoney & Rosen, 2005;Mevorach, 2010;Munoz, Peter, Herrmann, Wesselborg, & Lauber, 2010;Nagata, Hanayama, & Kawane, 2010;Nathan & Ding, 2010;Poon, Lucas, Rossi, & Ravichandran, 2014). Clearance of apoptotic cells is performed by two types of phagocytes, " professional phagocytes, " such as macrophages and immature dendritic cells, whose main function is phagocytosis, and " nonprofessional " neighboring cells that in addition to their defined functions in tissues are also able to perform phagocytosis redundant and highly evolutionarily conserved genetic pathways were identified . "
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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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