| First Author | Warnatsch A | Year | 2015 |
| Journal | Science | Volume | 349 |
| Issue | 6245 | Pages | 316-20 |
| PubMed ID | 26185250 | Mgi Jnum | J:225899 |
| Mgi Id | MGI:5694886 | Doi | 10.1126/science.aaa8064 |
| Citation | Warnatsch A, et al. (2015) Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349(6245):316-20 |
| abstractText | Secretion of the cytokine interleukin-1beta (IL-1beta) by macrophages, a major driver of pathogenesis in atherosclerosis, requires two steps: Priming signals promote transcription of immature IL-1beta, and then endogenous "danger" signals activate innate immune signaling complexes called inflammasomes to process IL-1beta for secretion. Although cholesterol crystals are known to act as danger signals in atherosclerosis, what primes IL-1beta transcription remains elusive. Using a murine model of atherosclerosis, we found that cholesterol crystals acted both as priming and danger signals for IL-1beta 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. |
