A novel mannose-binding lectin/ficolin-associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation

J Biol Chem. 2010 Mar 12;285(11):8234-43. doi: 10.1074/jbc.M109.065805. Epub 2010 Jan 6.

Abstract

The human lectin complement pathway involves circulating complexes consisting of mannose-binding lectin (MBL) or three ficolins (ficolin-1, -2, and -3) in association with three MBL/ficolin-associated serine proteases (MASP) (MASP-1, -2, and -3) and a nonenzymatic sMAP. MASP-1 and MASP-3 (MASP1 isoforms 1 and 2, respectively) are splice variants of the MASP1 gene, whereas MASP-2 and sMAP are splice variants of the MASP2 gene. We have identified a novel serum protein of 45 kDa that is associated with MBL and the ficolins. This protein is named MBL/ficolin-associated protein 1 (MAP-1 corresponding to MASP1 isoform 3). The transcript generating MAP-1 (MASP1_v3) contains exons 1-8 and a novel exon encoding an in-frame stop codon. The corresponding protein lacks the serine protease domains but contains most of the common heavy chain of MASP-1 and MASP-3. Additionally MAP-1 contains 17 unique C-terminal amino acids. By use of quantitative PCR and MAP-1-specific immunohistochemistry, we found that MAP-1 is highly expressed in myocardial and skeletal muscle tissues as well as in liver hepatocytes with a different expression profile than that observed for MASP-1 and MASP-3. MAP-1 co-precipitated from human serum with MBL, ficolin-2, and ficolin-3, and recombinant MAP-1 was able to inhibit complement C4 deposition via both the ficolin-3 and MBL pathway. In conclusion we have identified a novel 45-kDa serum protein derived from the MASP1 gene, which is highly expressed in striated muscle tissues. It is found in complex with MBL and ficolins and may function as a potent inhibitor of the complement system in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / physiology
  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • CHO Cells
  • Complement Activation / physiology*
  • Cricetinae
  • Cricetulus
  • Cross Reactions
  • Ficolins
  • Humans
  • Immunohistochemistry
  • Isomerism
  • Lectins / metabolism*
  • Mannose-Binding Lectins / metabolism*
  • Mannose-Binding Protein-Associated Serine Proteases / chemistry
  • Mannose-Binding Protein-Associated Serine Proteases / genetics*
  • Mannose-Binding Protein-Associated Serine Proteases / immunology
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Molecular Sequence Data
  • Molecular Weight
  • Muscle, Skeletal / metabolism*
  • Myocardium / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Lectins
  • Mannose-Binding Lectins
  • RNA, Messenger
  • MASP1 protein, human
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases