Pulmonary vascular injury in pancreatitis: evidence for a major role played by pancreatic elastase.
Using an experimental model of pancreatitis in the rat, the role of trypsin and elastase in mediating lung vascular injury in this condition was examined. The induction of pancreatitis by injection of sodium cholate in the pancreas resulted in a significant decrease in serum trypsin inhibitory capacity, and in a complete saturation of serum elastase inhibitory capacity matched by the appearance of endothelial injury of pulmonary capillaries and edema formation. The complete lack of serum elastase inhibitory capacity was associated with the presence of elastase activity in serum and bronchoalveolar lavage (BAL) fluids. The pretreatment of animals with N-furoyl saccharin (a potent inhibitor of many serine proteinases) prevented lung capillary injury and the imbalance of serum proteinase-anti-proteinase activities as well as the appearance of any elastolytic activity in serum and BAL fluids. These findings which clearly demonstrate the protease dependence of the pulmonary vascular injury in our experimental model, strongly suggested a major role for elastase(s). The suppression, in the experimental model, of the serum elastase inhibitory capacity by using chloramine-T resulted in an earlier onset of lung vascular damage, a marked worsening of pulmonary lesions, and an increase of elastolytic levels in serum and BAL fluids. Furthermore the physical properties of the protein molecule with enzyme activity detected in BAL fluids were consistent with those of rat pancreatic elastase. The reported data strongly support the hypothesis that pancreatic elastase plays a major role in the development of pulmonary vascular injury after acute pancreatitis.
D000818:Animals; D004195:Disease Models, Animal; D008168:Lung / Q000098:blood supply / Q000473:pathology*; D008297:Male; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism*; D010195:Pancreatitis / Q000201:enzymology / Q000473:pathology*; D011480:Protease Inhibitors / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014361:Trypsin Inhibitors / Q000097:blood
D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D010196:Pancreatic Elastase