title: Chemotactic peptide uptake in acute pancreatitis: correlation with tissue accumulation of leukocytes.
abstract: Chemotactic peptides bind specifically to receptors on leukocyte membranes. This property makes them prospective vehicles to evaluate inflammation and infection. We used two well-established models of acute pancreatitis to quantitate the binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine-lysine (fMLFK) to leukocytes and its correlation to degree of organ inflammation. Uptake of the (99m)Tc-labeled nicotinyl hydrazine-derivatized chemotactic peptide analog fMLFK-HYNIC was measured in blood, pancreas, lung, and muscle specimens in rats with edematous or necrotizing pancreatitis and was compared with neutrophil sequestration assessed by myeloperoxidase activity and histology. Chemotactic peptide uptake in the pancreas was increased in mild and severe pancreatitis compared with controls, with higher levels in severe than in mild disease, and correlated with tissue myeloperoxidase activity (r = 0.7395, P < 0.001). Increased pulmonary uptake only in severe pancreatitis reflected pancreatitis-induced neutrophil sequestration in the lungs. Muscle uptake was unchanged compared with controls. Edema formation did not affect chemotactic peptide uptake. The data suggest that uptake of chemotactic peptides can contribute to quantitative assessment of neutrophils in localized inflammatory processes and is independent of associated edema formation or microcirculatory compromise.
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hartwig
authors.forename: E A
authors.initials: EA
authors.lastname: Carter
authors.forename: R E
authors.initials: RE
authors.lastname: Jimenez
authors.forename: J
authors.initials: J
authors.lastname: Werner
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: C
authors.initials: C
authors.lastname: Fernandez-Del Castillo
authors.forename: A L
authors.initials: AL
authors.lastname: Warshaw
mesh_terms: D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism; D006651:Histocytochemistry; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D009539:Nicotinic Acids / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017556:Technetium Compounds / Q000378:metabolism
chemical_list: D009539:Nicotinic Acids; D009842:Oligopeptides; D017556:Technetium Compounds; C080396:trypsinogen activation peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; C049813:N-formylmethionyl-leucyl-phenylalanyl-lysine; D002108:Ceruletide; D009195:Peroxidase