Role of fibronectin in pancreatitis-associated lung injury.

Acute pancreatitis (AP) in humans can lead to increased vascular permeability in the lungs and respiratory failure. Fibronectin plays an important role in maintaining the structural integrity of the pulmonary epithelium and endothelium. However, its importance in pancreatitis-associated lung injury has not been defined. AP was produced by infusing caerulein (5 ug/kg/hr) in rats for 8 or 24 hr. Lung injury was assessed histologically and by determining lung microvascular permeability by bronchoalveolar lavage (BAL) analysis. Organ distribution of a target particle given intravenously was determined by the vascular clearance of magnetic iron oxide particles. Plasma fibronectin was measured by the enzyme-linked immunosorbent assay technique. After 8 hr of cerulein infusion, serum amylase increased 8-fold. Pancreatitis correlated with lung injury. BAL at 8 hr showed a 90% increase (P < 0.05) in albumin levels. Histological analysis at 8 hr revealed an increased number of leukocytes within the lungs. By 8 hr, plasma fibronectin significantly decreased 25% (P < 0.05) and the pulmonary uptake of iron oxide increased 111% (P < 0.05). By 24 hr, these effects had nearly resolved. These results indicate that decreases in serum fibronectin and increases in pulmonary leukocyte margination during acute pancreatitis may compromise the integrity of the air-blood barrier and also increase the pulmonary uptake of circulating pathogenic materials, thus making lung injury more likely.