Details

Autor(en) / Beteiligte

• Warnatsch, Annika
• Ioannou, Marianna
• Wang, Qian
• Papayannopoulos, Venizelos

Titel

Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis

Ist Teil von

• Science (American Association for the Advancement of Science), 2015-07, Vol.349 (6245), p.316-320

Ort / Verlag

Washington: American Association for the Advancement of Science

Erscheinungsjahr

2015

Quelle

Science Online

Beschreibungen/Notizen

• Secretion of the cytokine interleukin-1β (IL-1β) by macrophages, a major driver of pathogenesis in atherosclerosis, requires two steps: Priming signals promote transcription of immature IL-1β, and then endogenous "danger" signals activate innate immune signaling complexes called inflammasomes to process IL-1β for secretion. Although cholesterol crystals are known to act as danger signals in atherosclerosis, what primes IL-1β transcription remains elusive. Using a murine model of atherosclerosis, we found that cholesterol crystals acted both as priming and danger signals for IL-1β production. Cholesterol crystals triggered neutrophils to release neutrophil extracellular traps (NETs). NETs primed macrophages for cytokine release, activating T helper 17 (TH17) cells that amplify immune cell recruitment in atherosclerotic plaques. Therefore, danger signals may drive sterile inflammation, such as that seen in atherosclerosis, through their interactions with neutrophils.