Human CD14 mediates recognition and phagocytosis of apoptotic cells

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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.