title: 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 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.
authors.affiliation: University Department of Surgery, General Infirmary, Leeds, UK.
authors.forename: M
authors.initials: M
authors.lastname: Larvin
authors.forename: D J
authors.initials: DJ
authors.lastname: Alexander
authors.forename: S F
authors.initials: SF
authors.lastname: Switala
authors.forename: M J
authors.initials: MJ
authors.lastname: McMahon
mesh_terms: D000208:Acute Disease; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D010195:Pancreatitis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D010587:Phagocytosis; D014357:Trypsin / Q000097:blood*
chemical_list: D014357:Trypsin