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Updated: Jun 18, 2026
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Recognition of apoptotic cells by epithelial cells: conserved versus tissue-specific signaling responses
Vimal A Patel1, Daniel J Lee, Lanfei Feng
1Section of Nephrology, Department of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
Abstract:
During apoptosis, cells acquire new activities that enable them to modulate the fate and function of interacting phagocytes, particularly macrophages (m). Although the best known of these activities is anti-inflammatory, apoptotic targets also influence m survival and proliferation by modulating proximal signaling events, such as MAPK modules and Akt. We asked whether modulation of these same signaling events extends to epithelial cells, a minimally phagocytic cell type. We used BU.MPT cells, a mouse kidney epithelial cell line, as our primary model, but we also evaluated several epithelial cell lines of distinct tissue origins. Like m, mouse kidney epithelial cells recognized apoptotic and necrotic targets through distinct non-competing receptors, albeit with lower binding capacity and markedly reduced phagocytosis. Also, modulation of inflammatory activity and MAPK-dependent signaling by apoptotic and necrotic targets was indistinguishable in kidney epithelial cells and m. In contrast, modulation of Akt-dependent signaling differed dramatically between kidney epithelial cells and m. In kidney epithelial cells, modulation of Akt was linked to target cell recognition, independently of phagocytosis, whereas in m, modulation was linked to phagocytosis. Moreover, recognition of apoptotic and necrotic targets by kidney epithelial cells elicited opposite responses; apoptotic targets inhibited whereas necrotic targets stimulated Akt activity. These data confirm that nonprofessional phagocytes recognize and respond to dying cells, albeit in a manner partially distinct from m. By acting as sentinels of environmental change, apoptotic and necrotic targets may permit neighboring viable cells, especially non-migratory epithelial cells, to monitor and adapt to local stresses.
Insights
Epithelial cells, like macrophages, recognize dying cells. However, epithelial cells
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Apoptotic cells possess unique activities that influence phagocyte behavior, notably macrophages.
- Macrophases' functions, including survival and proliferation, are modulated by apoptotic cells via signaling pathways like MAPK and Akt.
- The extent to which these signaling events are modulated in non-phagocytic cells, such as epithelial cells, remains less understood.
Purpose of the Study:
- To investigate whether epithelial cells, despite limited phagocytic capacity, modulate signaling pathways (MAPK, Akt) in response to dying cells.
- To compare the responses of epithelial cells and macrophages to apoptotic and necrotic targets.
- To determine the role of target recognition versus phagocytosis in modulating Akt signaling in epithelial cells.
Main Methods:
- Utilized BU.MPT cells, a mouse kidney epithelial cell line, and other epithelial cell lines from diverse origins.
- Assessed the recognition and phagocytosis of apoptotic and necrotic targets by epithelial cells and macrophages.
- Analyzed the modulation of MAPK and Akt signaling pathways in response to target cell recognition and phagocytosis.
Main Results:
- Epithelial cells, similar to macrophages, recognize apoptotic and necrotic targets via distinct receptors, though with lower binding and phagocytosis efficiency.
- Modulation of inflammatory activity and MAPK signaling by dying cells was comparable between kidney epithelial cells and macrophages.
- Akt signaling modulation differed significantly: in epithelial cells, it was linked to target recognition (independent of phagocytosis), while in macrophages, it was linked to phagocytosis. Apoptotic targets inhibited Akt in epithelial cells, whereas necrotic targets stimulated it.
Conclusions:
- Nonprofessional phagocytes like epithelial cells can recognize and respond to dying cells, exhibiting distinct mechanisms compared to macrophages.
- Epithelial cells' responses to dying cells are linked to target recognition, with differential effects of apoptotic versus necrotic cells on Akt signaling.
- Dying cells act as sentinels, enabling epithelial cells to monitor and adapt to local environmental stresses.
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