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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Peptide Super-Agonist Enhances T-Cell Responses to Melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Complement Nomenclature-Deconvoluted

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Complement Nomenclature-Deconvoluted

    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.

OriginalsprogEngelsk
TidsskriftFrontiers in Immunology
Vol/bind9
Sider (fra-til)1945
ISSN1664-3224
DOI
StatusUdgivet - 2018

ID: 55413778