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MAp44, a Human Protein Associated with Pattern Recognition Molecules of the Complement System and Regulating the Lectin Pathway of Complement Activation¹

Søren E. Degn,^2* Annette G. Hansen,^* Rudi Steffensen, Christian Jacobsen, Jens C. Jensenius,^* and Steffen Thiel^*

^*Departments of Medical Microbiology and Immunology and Medical Biochemistry, University of Aarhus, Århus, Denmark; and Regional Centre for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Ålborg, Denmark

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 µg/ml in Ca²⁺-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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Lundbeck Foundation and the Danish Graduate School of Immunology (to S.E.D.).

² Address correspondence and reprint requests to Dr. Søren E. Degn, Department of Medical Microbiology and Immunology, The Bartholin Building, Wilhelm Meyers Allé 4, University of Aarhus, DK-8000 Århus C, Denmark. E-mail address: sdegn{at}microbiology.au.dk

³ Abbreviations used in this paper: sPRM, soluble pattern recognition molecule; CDS, coding sequence; EST, expressed sequence tag; GPC, gel permeation chromatography; HSA, human serum albumin; MASP, mannan-binding lectin-associated serine protease; MBL, mannan-binding lectin; MRP, MASP-related protein; NHS, normal human serum; pAb, polyclonal Ab; PRM, pattern recognition molecule; qRT-PCR, quantitative real-time RT-PCR; SPR, surface plasmon resonance; TRIFMA, time-resolved immunofluorometric assay; UTR, untranslated region.

⁴ The online version of this article contains supplemental material.

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The JI 2009 183: 6857-6858. [Full Text]