Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jul 25;38(2):147-60.
doi: 10.1016/j.devcel.2016.06.029.

The Dynamics of Apoptotic Cell Clearance

Michael R Elliott  1 , Kodi S Ravichandran  2
Affiliations
Review

The Dynamics of Apoptotic Cell Clearance

Michael R Elliott et al. Dev Cell. .

Abstract

The phagocytic clearance of dying cells in a tissue is a highly orchestrated series of intercellular events coordinated by a complex signaling network. Recent data from genetic, biochemical, and live-imaging approaches have greatly enhanced our understanding of the dynamics of cell clearance and how the process is orchestrated at the cellular and tissue levels. We discuss how networks regulating apoptotic cell clearance are integrated to enable a rapid, efficient, and high-capacity clearance system within tissues.

Keywords: apoptosis; chemotaxis; efferocytosis; imaging; immunity; phagocytosis; signal transduction.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Spatiotemporal characteristics of apoptotic cells
Generalized depiction of the temporal relationships among key features of apoptotic cells at different stages after induction of apoptosis. Effector caspase activation (i.e. caspases 3 and 7) and prominent morphological changes in apoptotic cells are shown in relationship to the accumulation of the four main find-me signals identified to date: ATP/UTP, CX3CL1, lysophosphatidycholine (LysoPC), and sphingosine-1-phosphate.
Figure 2
Figure 2. Model for hand-off of Rho signaling during transition from find-me to eat-me stages of efferocytosis
Detection of find-me signals by GPCR receptors on phagocytes stimulates migration and/or motility behavior in a manner dependent on RhoA and possibly Rac1 activation. During the find-me stage, some eat-me receptors, for example αvβ3/5 integrins, might function in adhesion and cell motility. Upon encountering the apoptotic target, adhesion receptors can function to recognize PtdSer on the surface of the apoptotic cells, either directly or indirectly via bridging proteins like MFG-E8 or Gas6, and reorient in a putative phagocytic synapse at the site of intercellular contact between the apoptotic cell and phagocyte. RhoA-GTP is likely inhibited or spatially confined during this stage to prevent antagonism with Rac that would impair Rac-GTP-dependent actin polymerization and phagocytic cup formation.
Figure 3
Figure 3. Different modes of phagocyte and apoptotic cell movement that can promote intercellular interaction and efferocytosis in a tissue
The four modes of efferocytosis related cell movements described are based on data from the indicated studies using intravital microscopy.
See this image and copyright information in PMC

References

    1. Arandjelovic S, Ravichandran KS. Phagocytosis of apoptotic cells in homeostasis. Nature Immunology. 2015;16:907–917. doi:10.1038/ni.3253. - PMC - PubMed
    1. Atkin-Smith GK, Tixeira R, Paone S, Mathivanan S, Collins C, Liem M, Goodall KJ, Ravichandran KS, Hulett MD, Poon IKH. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat Commun. 2015;6:7439. doi:10.1038/ncomms8439. - PMC - PubMed
    1. Bailey RW, Aronow B, Harmony JA, Griswold MD. Heat shock-initiated apoptosis is accelerated and removal of damaged cells is delayed in the testis of clusterin/ApoJ knock-out mice. Biol Reprod. 2002;66:1042–1053. - PubMed
    1. Baroni M, Pavani G, Marescotti D, Kaabache T, Borgel D, Gandrille S, Marchetti G, Legnani C, D'Angelo A, Pinotti M, Bernardi F. Membrane binding and anticoagulant properties of protein S natural variants. Thrombosis Research. 2010;125:e33–9. doi:10.1016/j.thromres.2009.09.015. - PubMed
    1. Basil MC, Levy BD. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat. Rev. Immunol. 2015 doi:10.1038/nri.2015.4. - PMC - PubMed

Publication types