Human CD14 mediates recognition and phagocytosis of apoptotic cells

Nature. 1998 Apr 2;392(6675):505-9. doi: 10.1038/33169.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Apoptosis / physiology*
  • Binding Sites
  • COS Cells
  • Cells, Cultured
  • Cloning, Molecular
  • Epitope Mapping
  • Epitopes, B-Lymphocyte / immunology
  • HL-60 Cells
  • Humans
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / physiology*
  • Lipopolysaccharides / metabolism
  • Macrophages / physiology
  • Phagocytosis / physiology*
  • Self Tolerance
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Monoclonal
  • Epitopes, B-Lymphocyte
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha