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

• 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0902388

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.