Figure 1.

NETs are critical mediators of murine and human acute pancreatitis (AP). Induction of pancreatitis with L-arginine resulted in an increase in amylase (A) and trypsin (B) activity in wild-type mice that was statistically diminished in PAD4^−/− mice, incapable of forming NETs. PAD4^−/− mice had significantly improved survival compared with wild type mice in recurrent L-arginine induced murine acute pancreatitis (median survival unreached vs. 15 days, p < 0.0001, n = 12 per group) (C). Patients with pancreatitis had elevated levels of circulating cell-free DNA (D) and MPO-DNA conjugates (E), biomarkers of NET formation that correlated with disease severity based on the revised Atlanta classification. ^*p < 0.05.