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  • de Boer, ElineUniv Oslo, Norway;Oslo Univ Hosp, Norway (författare)

Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • 2022-11-01
  • American Association of Immunologists,2022
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:lnu-119805
  • https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-119805URI
  • https://doi.org/10.4049/jimmunol.2101191DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were incubated with increasing concentrations of three classes of synthetic CpGs: CpG-A, -B, and -C oligodeoxynucleotides and their GpC sequence controls. Complement activation products were analyzed by immunoassays. Cytokine levels were determined via 27-plex beads-based immunoassay, and CpG interactions with individual complement proteins were evaluated using magnetic beads coated with CpG-B. In whole blood and plasma, CpG-B and CpG-C (p < 0.05 for both), but not CpG-A (p > 0.8 for all), led to time- and dose-dependent increase of soluble C5b-9, the alternative complement convertase C3bBbP, and the C3 cleavage product C3bc. GpC-A, -B, and -C changed soluble fluid-phase C5b-9, C3bBbP, and C3bc to the same extent as CpG-A, -B, and -C, indicating a DNA backbone-dependent effect. Dose-dependent CpG-B binding was found to C1q (r = 0.83; p 5 0.006) and factor H (r = 0.93; p < 0.001). The stimulatory complement effect was partly preserved in C2-deficient plasma and completely preserved in MASP-2-deficient serum. CpG-B increased levels of IL-1 beta, IL-2, IL-6, IL-8, MCP-1, and TNF in whole blood, which were completely abolished by inhibition of C5 and C5aR1 (p < 0.05 for all). In conclusion, synthetic analogs of bacterial and mitochondrial DNA activate the complement system via the DNA backbone. We suggest that CpG-B interacts directly with classical and alternative pathway components, resulting in complement-C5aR1-dependent cytokine release.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Sokolova, MarinaUniv Oslo, Norway;Oslo Univ Hosp, Norway (författare)
  • Quach, Huy Q.Univ Oslo, Norway;Oslo Univ Hosp, Norway,Linnaeus Ctr Biomat Chem, BMC (författare)
  • McAdam, Karin E.Univ Oslo, Norway;Oslo Univ Hosp, Norway (författare)
  • Gotz, Maximilian P.Univ Copenhagen, Denmark (författare)
  • Chaban, ViktoriiaUniv Oslo, Norway;Oslo Univ Hosp, Norway (författare)
  • Vaage, JarleUniv Oslo, Norway;Oslo Univ Hosp, Norway (författare)
  • Fagerang, BeatriceUniv Oslo, Norway;Oslo Univ Hosp, Norway (författare)
  • Woodruff, Trent M.Univ Queensland, Australia (författare)
  • Garred, PeterUniv Copenhagen, Denmark (författare)
  • Nilsson, Per H.,1980-Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Oslo Univ Hosp, Norway;Univ Oslo, Norway,Linnaeus Ctr Biomat Chem, BMC;HoRB(Swepub:lnu)enipe (författare)
  • Mollnes, Tom E.Univ Oslo, Norway;Oslo Univ Hosp, Norway;Nordland Hosp Bodo, Norway;Univ Tromso, Norway;Norwegian Univ Sci & Technol, Norway (författare)
  • Pischke, Soren E.Univ Oslo, Norway;Oslo Univ Hosp, Norway (författare)
  • Univ Oslo, Norway;Oslo Univ Hosp, NorwayLinnaeus Ctr Biomat Chem, BMC (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Immunology: American Association of Immunologists209:9, s. 1760-17670022-17671550-6606

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