Impaired Mononuclear Phagocyte Function in Patients with Severe Acute Pancreatitis: Evidence from Studies of Plasma Clearance of Trypsin and Monocyte Phagocytosis

Activated proteases in plasma are complexed by alpha 2-macroglobulin. Although the complexes retain peptidase activity, they are usually eliminated promptly by mononuclear phagocytes. In severe acute pancreatitis, almost 30% of plasma alpha 2-macroglobulin becomes complexed, suggesting impaired clearance. In the present study, plasma [methyl-14C]trypsin clearance and monocyte phagocytosis were investigated. Attacks complicated by major organ-system failure, pancreatic pseudocyst, abscess, or necrosis were graded severe (median Ranson score 5.5). Plasma [methyl-14C]trypsin half-life was significantly increased in severe attacks (N = 7, median 21.1 min), compared to mild attacks (N = 14, median 15.4 min, P < 0.05) and healthy controls (N = 4, median 10.8 min, P < 0.02). Monocyte phagocytosis was significantly lower in severe attacks (N = 9, median 3.6%) compared to mild attacks (N = 20, median 20.8%, P < 0.01) and healthy controls (N = 8, median 26.9%, P < 0.01). Plasma [methyl-14C]trypsin half-life and monocyte phagocytosis were significantly inversely correlated (r = -0.51, P < 0.01). Impaired clearance of circulating trypsin in acute pancreatitis is potentially deleterious but may be reversed by stimulating mononuclear phagocytes.