Diminished lung injury with vascular adhesion molecule-1 blockade in choline-deficient ethionine diet-induced pancreatitis

• Published in: Surgery 2003-02, Vol.133 (2), p.186-196
• Main Authors: Callicutt, Christopher S., Sabek, Omaima, Fukatsu, Kazuhiko, Lundberg, Andrew H., Gaber, Lillian, Wilcox, Henry, Kotb, Malak, Gaber, A.Osama
• Format: Article
• Language: English
• Subjects: Acute Disease; Amylases - blood; Animals; Antibodies, Monoclonal - pharmacology; Apoptosis; Biological and medical sciences; Choline - pharmacology; Diet; Ethionine - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Immunohistochemistry; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lung - enzymology; Lung - immunology; Lung - pathology; Medical sciences; Mice; Other diseases. Semiology; Pancreas - pathology; Pancreatitis - complications; Pancreatitis - immunology; Pancreatitis - pathology; Peroxidase - metabolism; Pneumonia - etiology; Pneumonia - immunology; Pneumonia - pathology; Up-Regulation; Vascular Cell Adhesion Molecule-1 - immunology; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1067/msy.2003.84

Background. Lung injury in severe acute pancreatitis is mediated by infiltrating leukocytes. Our laboratory has previously demonstrated that acute lung injury in acute pancreatitis results in an up-regulation of vascular adhesion molecule-1 (VCAM-1) cell surface receptor expression on pulmonary vascular endothelium and neutrophil sequestration. The objective of this study was to determine whether blocking expression of VCAM-1 in acute pancreatitis would modify acute pulmonary injury. Methods. Young female mice were fed a choline-deficient ethionine (CDE) supplemented diet to induce acute pancreatitis. After initiation of the diet, one group (acute pancreatitis treated [n = 18]) was treated with blocking doses (2.35 mg/kg) of monoclonal anti-VCAM-1 receptor antibody (Ab) at 48, 96, and 120 hours. A second group (acute pancreatitis treated control [n = 5]) was treated with a similar dose of an isotypic control for VCAM-1 (nonbinding Ab) at the same time points. A third group (acute pancreatitis untreated [n = 12]) received a CDE diet, and a fourth group (control [n = 11]) received standard food with no Ab treatment. All animals were killed at 144 hours. The dual radiolabeled monoclonal Ab method was used to quantitate VCAM-1 cell surface expression in lung tissue. Lung injury was assessed histologically, and apoptosis was detected by transferase-mediated deoxyuridine triphosphate nick end labeling assay. Pulmonary leukocyte sequestration was determined by myeloperoxidase (MPO) assay and CD18 staining. Results. Pulmonary VCAM-1 cell surface expression was significantly increased in animals with acute pancreatitis when compared to controls (P