Impaired mononuclear phagocyte function in patients with severe acute pancreatitis: Evidence from studies of plasma clearance of trypsin and monocyte phagocytosis

Abstract
Activated proteases in plasma are complexed by α2-macroglobulin. Although the complexes retain peptidase activity, they are usually eliminated promptly by mononuclear phagocytes. In severe acute pancreatitis, almost 30% of plasma α2-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 (media 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,PN=4, median 10.8 min,PN=9, median 3.6%) compared to mild attacks (N=20, median 20.8%,PN=8, median 26.9%,Pmethyl-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.