Characterization of the interaction between collectin 11 (CL-11, CL-K1) and nucleic acids

Mol Immunol. 2013 Dec;56(4):757-67. doi: 10.1016/j.molimm.2013.07.011. Epub 2013 Aug 14.

Abstract

Collectins are a group of innate immune proteins that contain collagen-like regions and globular C-type lectin domains. Via the lectin domains, collectins recognize and bind to various microbial carbohydrate patterns. Collectin 11 (CL-11) exists in complex with the complement activating MBL-associated proteases, MASPs. In the present work, we characterize the interaction between CL-11 and DNA, and show that CL-11 binds to DNA from a variety of origins in a calcium-independent manner. CL-11 binds also to apoptotic cells presenting extracellular DNA on their surface. The binding to DNA is sensitive to changes in ionic strength and pH. Competition studies show that CL-11 binds to nucleic acids and carbohydrates via separate binding-sites and oligomericity appears crucial for binding activity. Combined interaction with DNA and mannan strongly increases binding avidity. By surface plasmon resonance we estimate the dissociation constant for the binding between CL-11 and double stranded DNA oligonucleotides to K(D)=9-20 nM. In an in vitro assay we find that CL-11 binds to DNA coated surfaces, which leads to C4b deposition via MASP-2. We propose that CL-11, e.g. via complement, may play a role in response to particles and surfaces presenting extracellular DNA, such as apopototic cells, neutrophil extracellular traps and biofilms.

Keywords: CL-11; CRD; Collectin; Collectin 11 (alias Collectin Kidney 1, CL-K1); Complement; Extracellular DNA; Innate immunity; MASP; MBL; MBL-associated serine protease; RU; SP-A/-D; SPR; carbohydrate recognition domain; mannan-binding lectin; resonance unit; surface plasmon resonance; surfactant protein A/D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • CHO Cells
  • Calcium / metabolism
  • Collectins / genetics
  • Collectins / metabolism*
  • Complement C4b / metabolism
  • Cricetinae
  • Cricetulus
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism*
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / radiation effects
  • Mannans / metabolism
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Monosaccharides / metabolism
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism*
  • Osmolar Concentration
  • Protein Binding
  • Recombinant Proteins / metabolism*
  • Surface Plasmon Resonance
  • Ultraviolet Rays

Substances

  • Collectins
  • DNA, Bacterial
  • Mannans
  • Monosaccharides
  • Oligonucleotides
  • Recombinant Proteins
  • collectin CL-K1, human
  • Complement C4b
  • DNA
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases
  • Calcium