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Jens Christian Jensenius

MAp19, the alternative splice product of the MASP2 gene

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The lectin pathway of complement is a central part of innate immunity, but as a powerful inducer of inflammation it needs to be tightly controlled. The MASP2 gene encodes two proteins, MASP-2 and MAp19. MASP-2 is the serine protease responsible for lectin pathway activation. The smaller alternative splice product, MAp19, lacks a catalytic domain but retains two of three domains involved in association with the pattern-recognition molecules (PRMs): mannan-binding lectin (MBL), H-ficolin, L-ficolin and M-ficolin. MAp19 reportedly acts as a competitive inhibitor of MASP-2-mediated complement activation. In light of a ten times lower affinity of MAp19, versus MASP-2, for association with the PRMs, much higher serum concentrations of MAp19 than MASP-2 would be required for MAp19 to exert such an inhibitory activity. Just four amino acid residues distinguish MAp19 from MASP-2, and these are conserved between man, mouse and rat. Nonetheless we generated monoclonal rat anti-MAp19 antibodies and established a quantitative assay. We found the concentration of MAp19 in serum to be 217 ng/ml, i.e., 11nM, comparable to the 7 nM of MASP-2. In serum all MASP-2, but only a minor fraction of MAp19, was associated with PRMs. In contrast to previous reports we found that MAp19 could not compete with MASP-2 for binding to MBL, nor could it inhibit MASP-2-mediated complement activation. Immunohistochemical analyses combined with qRT-PCR revealed that both MAp19 and MASP-2 were mainly expressed in hepatocytes. High levels of MAp19 were found in urine, where MASP-2 was absent.
Original languageEnglish
JournalJournal of Immunological Methods
Volume373
Issue1-2
Pages (from-to)89-101
Number of pages13
ISSN0022-1759
DOIs
Publication statusPublished - 2011

    Research areas

  • Alternative Splicing, Animals, Antibodies, Monoclonal, Antibody Affinity, Blotting, Western, Cytoplasm, Gene Expression Profiling, HEK293 Cells, Hepatocytes, Humans, Hybridomas, Immunohistochemistry, Kidney, Lectins, Macrophages, Alveolar, Mannose-Binding Lectin, Mannose-Binding Protein-Associated Serine Proteases, Mice, Protein Binding, Protein Isoforms, Rats, Reverse Transcriptase Polymerase Chain Reaction

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