The first histological demonstration of pancreatic oxidative stress in human acute pancreatitis.

摘要

Necrotizing acute pancreatitis is associated with an inflammatory explosion involving numerous pro-inflammatory mediator cascades and oxidative stress. Acinar oxygen free radical production aggravates pancreatic tissue damage, and promotes cellular adhesion molecule upregulation resulting in leukocyte adherence and activation. The cerium capture oxygen free radical histochemistry combined with reflectance confocal laser scanning microscopy allows the "in situ" histological demonstration of oxygen free radical formation in live tissues. Here we present a case report, where oxidative stress is demonstrated on a histological level for the first time in human acute pancreatitis. A 44-year-old male patient suffering from acute exacerbation of his chronic pancreatitis developed a pancreato-pleural fistula with amylase-rich left pleural exudate causing respiratory compromise. Subsequent to an urgent thoracic decompression a distal pancreatectomy and splenectomy was performed with the closure of abdomino-thoracic fistula. The postoperative course was uneventful, except for a transient pancreatico-cutaneous fistula, which healed after conservative treatment. To carry out cerium capture oxygen free radical histochemistry the resected pancreas specimen was readily perfused with cerium-chloride solution through the arteries on the resection surface. Frozen sections were cut, E-, P-selectin, ICAM and VCAM were labeled by immunofluorescence. The tumor-free margin of an identically treated pancreas carcinoma specimen served as a control. Intrapancreatic oxidative stress and cellular adhesion molecule expression were detected by confocal laser scanning microscopy. Numerous pancreatic acini and neighboring capillaries showed oxygen free radical-derived cerium-perhy-droxide depositions corresponding to strong local oxidative stress. Acinar cytoplasmic reflectance signals suggested xanthine-oxidase as a source of oxygen free radicals. These areas presented considerably increased endothelial P-selectin expression with adherent, oxygen free radical-producing polymorphonuclear leukocytes displaying pericellular cerium-reflectance. Modest ICAM upregulation was noted, E-selectin and VCAM expression was negligible. The control pancreas specimen showed minimal oxidative stress with weak, focal P-selectin expression. The development of deleterious pancreatic oxidative stress was based on indirect evidence in human acute pancreatitis. To the best of our knowledge this is the first report demonstrating persistent intrapancreatic oxidative stress histologically in human acute pancreatitis. We have noted P-selectin overexpression with a preponderance in the areas of acinar oxidative stress.