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Human CD14 mediates recognition and phagocytosis of apoptotic cells
A Devitt1, O D Moffatt, C Raykundalia
1Department of Immunology, University of Birmingham Medical School, UK.
Abstract:
Cells undergoing programmed cell death (apoptosis) are cleared rapidly in vivo by phagocytes without inducing inflammation. Here we show that the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 on the surface of human macrophages is important for the recognition and clearance of apoptotic cells. CD14 can also act as a receptor that binds bacterial lipopolysaccharide (LPS), triggering inflammatory responses. Overstimulation of CD14 by LPS can cause the often fatal toxic-shock syndrome. Here we show that apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic cells. This interaction depends on a region of CD14 that is identical to, or at least closely associated with, a region known to bind LPS. However, apoptotic cells, unlike LPS, do not provoke the release of pro-inflammatory cytokines from macrophages. These results indicate that clearance of apoptotic cells is mediated by a receptor whose interactions with 'non-self' components (LPS) and 'self' components (apoptotic cells) produce distinct macrophage responses.
Insights
Macrophages use CD14 to clear apoptotic cells without inflammation. This receptor distinguishes between self (apoptotic cells) and non-self (LPS) signals, preventing harmful inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Phagocytes rapidly clear apoptotic cells in vivo, a process crucial for tissue homeostasis and preventing inflammation.
- CD14, a glycosylphosphatidylinositol-linked plasma-membrane glycoprotein on macrophages, is known to bind bacterial lipopolysaccharide (LPS) and trigger inflammatory responses.
Purpose of the Study:
- To investigate the role of CD14 in the recognition and clearance of apoptotic cells by macrophages.
- To determine whether CD14's interaction with apoptotic cells elicits an inflammatory response.
Main Methods:
- Utilized human macrophages to study interactions with apoptotic cells.
- Investigated the binding region of CD14 involved in apoptotic cell recognition.
- Assessed the release of pro-inflammatory cytokines following CD14 engagement with apoptotic cells and LPS.
Main Results:
- Demonstrated that CD14 mediates the recognition and phagocytosis of apoptotic cells by macrophages.
- Identified that the LPS-binding region of CD14 is involved in apoptotic cell interaction.
- Showed that apoptotic cells, unlike LPS, do not induce pro-inflammatory cytokine release from macrophages.
Conclusions:
- CD14 acts as a dual-function receptor, mediating both the clearance of apoptotic cells and the inflammatory response to LPS.
- The distinct responses triggered by apoptotic cells and LPS highlight a sophisticated mechanism for maintaining immune homeostasis.
- This finding reveals a novel pathway for the immunomodulatory clearance of cellular debris.