Immunoregulation of Neutrophil Extracellular Trap Formation by Endothelial-Derived p33 (gC1q Receptor)

Ariane Neumann, Praveen Papareddy, Johannes Westman, Ole Hyldegaard, Johanna Snäll, Anna Norrby-Teglund, Heiko Herwald

Research output: Contribution to journalArticlepeer-review


The formation of neutrophil extracellular traps (NETs) is a host defence mechanism, known to facilitate the entrapment and growth inhibition of many bacterial pathogens. It has been implicated that the translocation of myeloperoxidase (MPO) from neutrophilic granules to the nucleus is crucial to this process. Under disease conditions, however, excessive NET formation can trigger self-destructive complications by releasing pathologic levels of danger-associated molecular pattern molecules (DAMPs). To counteract such devastating immune reactions, the host has to rely on precautions that help circumvent these deleterious effects. Though the induction of DAMP responses has been intensively studied, the mechanisms that are used by the host to down-regulate them are still not understood. In this study, we show that p33 is an endothelial-derived protein that has the ability to annul NET formation. We found that the expression of human p33 is up-regulated in endothelial cells upon infections with Streptococcus pyogenes bacteria. Using tissue biopsies from a patient with streptococcal necrotising fasciitis, we monitored co-localisation of p33 with MPO. Further in vitro studies revealed that p33 is able to block the formation of DAMP-induced NET formation by inhibiting the enzymatic activity of MPO. Additionally, mice challenged with S. pyogenes bacteria demonstrated diminished MPO activity when treated with p33. Together, our results demonstrate that host-derived p33 has an important immunomodulating function that helps to counterbalance an overwhelming DAMP response.

Original languageEnglish
Pages (from-to)30-43
JournalJournal of Innate Immunity
Issue number1
Publication statusPublished - 2018

Subject classification (UKÄ)

  • Microbiology in the medical area

Free keywords

  • <italic>Streptococcus pyogenes</italic> infection
  • Danger-associated molecular pattern molecules
  • Innate immunity
  • Neutrophil extracellular traps


Dive into the research topics of 'Immunoregulation of Neutrophil Extracellular Trap Formation by Endothelial-Derived p33 (gC1q Receptor)'. Together they form a unique fingerprint.

Cite this