Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital

Chimeric Proteins Containing MAP-1 and Functional Domains of C4b-Binding Protein Reveal Strong Complement Inhibitory Capacities

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. Long-Term Exposure to Inflammation Induces Differential Cytokine Patterns and Apoptosis in Dendritic Cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Fatal pneumococcus meningitis in a child with complement factor ficolin-3 deficiency

    Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

  2. Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The impact of mannose-binding lectin polymorphisms on lung function in primary ciliary dyskinesia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

The complement system is a tightly regulated network of proteins involved in defense against pathogens, inflammatory processes, and coordination of the innate and adaptive immune responses. Dysregulation of the complement cascade is associated with many inflammatory disorders. Thus, inhibition of the complement system has emerged as an option for treatment of a range of different inflammatory diseases. MAP-1 is a pattern recognition molecule (PRM)-associated inhibitor of the lectin pathway of the complement system, whereas C4b-binding protein (C4BP) regulates both the classical and lectin pathways. In this study we generated chimeric proteins consisting of MAP-1 and the first five domains of human C4BP (C4BP1-5) in order to develop a targeted inhibitor acting at different levels of the complement cascade. Two different constructs were designed and expressed in CHO cells where MAP-1 was fused with C4BP1-5 in either the C- or N-terminus. The functionality of the chimeric proteins was assessed using different in vitro complement activation assays. Both chimeric proteins displayed the characteristic Ca2+-dependent dimerization and binding to PRMs of native MAP-1, as well as the co-factor activity of native C4BP. In ELISA-based complement activation assays they could effectively inhibit the lectin and classical pathways. Notably, MAP-1:C4BP1-5 was five times more effective than rMAP-1 and rC4BP1-5 applied at the same time, emphasizing the advantage of a single inhibitor containing both functional domains. The MAP-1/C4BP chimeras exert unique complement inhibitory properties and represent a novel therapeutic approach targeting both upstream and central complement activation.

TidsskriftFrontiers in Immunology
Sider (fra-til)1945
StatusUdgivet - 2018

ID: 55413778