Ficolin-2 recognizes DNA and participates in the clearance of dying host cells

Mol Immunol. 2007 Feb;44(5):856-65. doi: 10.1016/j.molimm.2006.04.002. Epub 2006 May 26.

Abstract

Ficolin-2 is a serum opsonin, which has been shown to be a pattern recognition molecule in the lectin complement activation pathway. Because innate immune mechanisms are involved in maintaining tissue homeostasis we hypothesized that Ficolin-2 also participate in the clearance of dying host cells. We found that Ficolin-2 binds to late apoptotic cells, as well as to apoptotic bodies and necrotic cells, but not to early apoptotic cells. We demonstrated that Ficolin-2 binds DNA in a calcium dependent manner and that DNA inhibits the binding to late apoptotic and necrotic cells, suggesting that DNA on permeable dying cells is a plausible ligand. Reconstituting serum deficient of Ficolin-2, C1q and mannose-binding lectin with Ficolin-2 augmented deposition of complement C4 on necrotic cells. Opsonization leads to an enhanced attachment/uptake of necrotic cells by macrophages. In conclusion dying host cells expose ligands with the capacity of binding Ficolin-2, which in turn leads to increased attachment and engulfment. Binding of Ficolin-2 to DNA points at nucleic acid exposed by permeable late apoptotic and necrotic cells as one of the ligands for Ficolin-2. Ficolin-2 may therefore be a scavenger molecule participating in the removal of host cells and maintenance of tissue homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / immunology*
  • CHO Cells
  • Complement Activation / drug effects
  • Cricetinae
  • Cricetulus
  • DNA / metabolism*
  • Humans
  • Jurkat Cells
  • Lectins / genetics
  • Lectins / metabolism
  • Lectins / pharmacology*
  • Monocytes / drug effects
  • Monocytes / immunology
  • Necrosis / immunology*
  • Opsonin Proteins / genetics
  • Opsonin Proteins / metabolism
  • Opsonin Proteins / pharmacology*
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Antibodies, Monoclonal
  • Lectins
  • Opsonin Proteins
  • Recombinant Proteins
  • ficolin
  • DNA