Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex

J Innate Immun. 2013;5(3):242-50. doi: 10.1159/000345356. Epub 2012 Dec 4.

Abstract

Collectins and ficolins are important in the clearance of endogenous and exogenous danger materials. A new human collectin-11 was recently identified in low concentration in serum in complex with mannose-binding lectin (MBL)/ficolin-associated serine proteases. Collectin-11 binds to carbohydrate residues present on various microorganisms. Thus, we hypothesized that collectin-11 could be a novel initiation molecule in the lectin pathway of complement. We can show that collectin-11 associates with all the known MBL-associated serine proteases (MASP-1, MASP-2 and MASP-3) as well as the lectin complement pathway regulator MAP-1. Furthermore, we found that complex formation between recombinant collectin-11 and recombinant MASP-2 on Candida albicans leads to deposition of C4b. Native collectin-11 in serum mediated complement activation and deposition of C4b and C3b, and formation of the terminal complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway in addition to MBL, ficolin-1, ficolin-2 and ficolin-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / immunology*
  • Candida albicans / metabolism
  • Complement C3b / immunology
  • Complement C3b / metabolism
  • Complement C4b / immunology
  • Complement C4b / metabolism
  • Complement Pathway, Mannose-Binding Lectin / immunology*
  • Humans
  • Lectins / immunology
  • Lectins / metabolism
  • Mannose-Binding Lectin / immunology*
  • Mannose-Binding Lectin / metabolism
  • Mannose-Binding Protein-Associated Serine Proteases / immunology*
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Multiprotein Complexes / immunology*
  • Multiprotein Complexes / metabolism

Substances

  • Lectins
  • Mannose-Binding Lectin
  • Multiprotein Complexes
  • ficolin
  • Complement C3b
  • Complement C4b
  • Mannose-Binding Protein-Associated Serine Proteases