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Human CD14 mediates recognition and phagocytosis of apoptotic cells

Abstract

Cells undergoing programmed cell death (apoptosis) are cleared rapidly in vivo by phagocytes without inducing inflammation1. Here we show that the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 (refs 2, 3) 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 responses4. Overstimulation of CD14 by LPS can cause the often fatal toxic-shock syndrome5,6. 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.

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Figure 1: CD14 carries the epitope defined by monoclonal antibody 61D3.
Figure 2: CD14-mediated recognition and phagocytosis of apoptotic cells by macrophages.
Figure 3: Role of CD14 in recognition and phagocytosis of apoptotic cells.
Figure 4: Epitope mapping of the 61D3 monoclonal antibody by ELISA, using immobilized soluble recombinant CD14-Fc fusion protein.
Figure 5: Production of TNF-α by macrophages stimulated with LPS but not apoptotic cells.

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Acknowledgements

This work was supported by the MRC.

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Correspondence to Christopher D. Gregory.

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Devitt, A., Moffatt, O., Raykundalia, C. et al. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 392, 505–509 (1998). https://doi.org/10.1038/33169

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