Investigations on collectin liver 1

J Biol Chem. 2013 Aug 9;288(32):23407-20. doi: 10.1074/jbc.M113.492603. Epub 2013 Jun 27.

Abstract

Collectins are pattern recognition molecules of the innate immune system showing binding to carbohydrate structures on microorganisms in a calcium-dependent manner. Recently, three novel collectins, collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1 and CL-11), and collectin placenta 1 (CL-P1), were discovered. The roles of these three collectins remain largely unknown. Here, we present a time-resolved immunofluorometric assay for quantification of CL-L1. The concentration of CL-L1 in donor plasma (n = 210) was distributed log-normally with a median value of 3.0 μg/ml (range 1.5-5.5 μg/ml). We observed on average 30% higher concentrations of CL-L1 in plasma as compared with serum. Size analysis by gel-permeation chromatography showed CL-L1 in serum to elute as large 700-800-kDa complexes and smaller 200-300-kDa complexes. CL-L1 showed specific binding to mannose-TSK beads in a Ca(2+)-dependent manner. This binding could be inhibited by mannose and glucose, but not galactose, indicating that CL-L1 binds via its carbohydrate-recognition domain and has ligand specificity similar to that of mannan-binding lectin. Western blot analysis of CL-L1 showed the presence of several oligomeric forms in serum. Ontogeny studies showed CL-L1 to be present at birth at near adult levels. CL-L1 levels exhibit low variation in healthy adults over a 1-year period. During acute-phase responses, the CL-L1 levels display only minor variations. In serum, CL-L1 was found in complexes with mannan-binding lectin-associated serine proteases, suggesting a role in the lectin pathway of complement activation. The presented data establish a basis for future studies on the biological role of CL-L1.

Keywords: Collectins; Complement System; Inflammation; Innate Immunity; Lectin.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Collectins / blood*
  • Complement Pathway, Mannose-Binding Lectin / physiology
  • Female
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • HEK293 Cells
  • Hexoses / blood
  • Humans
  • Male
  • Protein Multimerization*
  • Serum / metabolism*

Substances

  • COLEC10 protein, human
  • Collectins
  • Hexoses