Roles of polymorph nuclear neutrophil elastase and thrombomodulin in patients with acute pancreatitis in the context of neutrophil extracellular traps

Abstract

The goal of the study was to evaluate progression of acute pancreatitis (AP) based on measurement of plasma levels of polymorph nuclear neutrophil (PMN) elastase, thrombomodulin (TM), lipopolysaccharide (LPS), thrombin-antithrombin III complex (TAT), and platelet counts associated with neutrophil extracellular trap (NETs). The subjects were 42 patients with AP, including 30 classified with mild AP (MAP) and 12 with severe AP (SAP), and 20 normal adult controls. Plasma levels of TM, PMN elastase, LPS, and TAT were measured by ELISA. Platelets were measured by a routine method. TM molecular subspecies were isolated from plasma using beads and analyzed by reverse-phase HPLC. After these measurements, ulinastatin was administered to 16 patients. TM, PMN elastase, LPS, and TAT levels in patients with AP were significantly higher than those in controls. Furthermore, these four markers were significantly higher in SAP cases than in MAP cases. Platelet counts significantly decreased in the order of SAP, MAP, and controls. Eight TM subspecies were present in plasma and most of these increased with aggravation of AP. The areas under the ROC curves for PMN elastase, TM, LPS, and TAT were 0.814, 0.827, 0.766, and 0.860, respectively. The markers were normalized by ulinastatin treatment in 16 patients with AP. At onset of focal AP, PMN elastase accumulates in platelets and leukocytes in NETs, and is released from neutrophils. This then releases TM from blood vessel walls, which activates coagulation and leads to systemic aggregation. Treatment with ulinastatin is effective for this disorder.