4:10 pm to 5:00 pm
Autodigestion and Inflammation
Digestive Enzymes on the Prowl
Clinical evidence indices that all diseases are accompanied by markers for inflammation. The inflammatory cascade serves as a tissue repair mechanism after an injury. Thus the clinical evidence raises the question about the mechanism(s), which causes injury to a tissue/organ and therefore triggers the inflammatory cascade. This important problem is the focus of our research. There are well-recognized tissue injury mechanisms, for example due to infections (bacterial, viral etc.), mechanical trauma (stress waves, fractures, etc.), elevated or reduced temperatures (burns, cold exposures, etc.) or various chemical exposures. But in many non-infectious inflammatory conditions and diseases the injury mechanisms have not been identified.
We propose here a previously unrecognized mechanism that causes injury to tissue due to pancreatic digestive enzymes in the digestive track. These powerful enzymes, required for normal digestion, are synthesized in the pancreas and transported into the lumen of the small intestine where they are fully activated in order to break down biological molecules in food. The epithelial mucosal barrier and its associated mucin layer prevent escape of the digestive enzymes into the wall of the intestine. But if the mucosal barrier allows leakage of digestive enzymes into the wall of the intestine, the intestinal villi and other parts of the intestinal wall are digested, the digestive enzymes leak into the systemic circulation and cause cleavage of plasma and membrane proteins with loss of their physiological functions. We present evidence in hemorrhagic and septic shock that autodigestion is the predominant cause of cell/organ dysfunction, tissue lesion formation, acute respiratory distress, heart failure and death. Blockade of pancreatic digestive enzymes inside the lumen of the small intestine serves to minimize autodigestion in experimental forms of shock and significantly improves cell and organ dysfunctions. These results suggest that the pancreatic digestive enzymes may play a central role in disease and death and may be a price to pay for the lifelong ability to digest.
Supported by GM 85072 and a gift from Leading Biosciences Inc., San Diego, CA.
Refreshments will be served prior to the talk.