Endogenous PTX3 translocates at the membrane of late apoptotic human neutrophils and is involved in their engulfment by macrophages

Cell Death Differ. 2009 Mar;16(3):465-74. doi: 10.1038/cdd.2008.173. Epub 2008 Dec 12.

Abstract

Neutrophils are short-lived innate immune cells that rapidly die by apoptosis. A rapid and efficient clearance of apoptotic cells is crucial to avoid autoimmunity. This process involves cell alterations, endocytic receptors expressed by phagocytic cells and soluble bridging molecules (opsonins) that facilitate internalization of apoptotic cells by phagocytes. Neutrophils constitutively express the prototypic long pentraxin PTX3 that binds to apoptotic cells and modulates their clearance. We thus evaluated whether endogenous PTX3 may interfere with the capture of apoptotic neutrophils. We observed that PTX3 accumulates in blebs at the surface of late apoptotic neutrophils, resulting from its active translocation from granules to the membrane. A neutralizing anti-PTX3 monoclonal Ab (mAb) inhibits the capture of late apoptotic neutrophils by macrophages. This study shows that intracellular PTX3 translocates at the surface of late apoptotic neutrophils and acts as an 'eat-me' molecule for their recognition and capture by macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cell Membrane / metabolism
  • Humans
  • Macrophages / cytology
  • Macrophages / physiology*
  • Neutrophils / cytology
  • Neutrophils / metabolism*
  • Phagocytosis / physiology*
  • Protein Transport
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism*

Substances

  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein