Pancreatic enzyme mechanisms that trigger physiological shock and high mortality

Abstract

Non-infectious inflammation is encountered in many human diseases. One of the strongest forms of inflammations occurs in physiological shock, a condition with high levels of cardiovascular cell activation, failure in the function of multiple organs and high mortality. We previously reported that pancreatic digestive proteases might be generating inflammatory peptides from proteins, in part extra-cellular matrix proteins, located in the wall of the intestine. To identify which particular pancreatic enzymes may be triggering the production of inflammatory activators in shock, the pancreatic serine proteases trypsin, chymotrypsin, and elastase were reacted with supernatants of homogenized intestines and hearts from Wistar rats and tested for their ability to activate neutrophils, a non-specific immune cell type involved in acute inflammation. All three proteases served to generate neutrophil activators from the intestine and the heart. Moreover, we found that elastase reacted with heart supernatant produced a level of inflammatory stimulation that caused not only cell activation but also direct neutrophil necrosis. We conclude that pancreatic serine proteases may represent key players during the rapid organ failure encountered in shock.