MAp44, a Human Protein Associated with Pattern Recognition Molecules of the Complement System and Regulating the Lectin Pathway of Complement Activation

Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 microg/ml in Ca(...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2009-12, Vol.183 (11), p.7371-7378
Main Authors: Degn, Soren E, Hansen, Annette G, Steffensen, Rudi, Jacobsen, Christian, Jensenius, Jens C, Thiel, Steffen
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Complement Activation
Electrophoresis, Polyacrylamide Gel
Ficolins
Humans
Isoenzymes - genetics
Isoenzymes - metabolism
Lectins - metabolism
Mannose-Binding Lectin - metabolism
Mannose-Binding Protein-Associated Serine Proteases - genetics
Mannose-Binding Protein-Associated Serine Proteases - metabolism
Molecular Sequence Data
Phylogeny
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Surface Plasmon Resonance
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 microg/ml in Ca(2+)-dependent complexes with the soluble pattern recognition molecules. The affinity for MBL is in the nanomolar range (K(D) = 0.6 nM) as determined by surface plasmon resonance. The first eight exons of the gene for MAp44 encode four domains shared with MBL-associated serine protease (MASP)-1 and MASP-3 (CUB1-EGF-CUB2-CCP1), and a ninth exon encodes C-terminal 17 aa unique to MAp44. mRNA profiling in human tissues shows high expression in the heart. MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0902388