Our understanding of the early events which occur during the evolution of pancreatitis has been hampered by the variable and complex nature of the disease as it occurs clinically as well as the relative inaccessibility of the pancreas to morphological and biochemical monitoring. To overcome these problems, we and other investigators have turned to experimental models of acute pancreatisis which, to varying degrees, resemble the clinical disease. In addition, chronic pancreatitis has been examined in humans, but only long after the disease has become established. As noted in this review, recent findings cast doubt on the previously held concept that proteolytic enzymes are activated within the pancreatic duct or intercellular space. Rather, they suggest that early during the course of acute pancreatitis this activation may occur within the pancreatic acinar cell itself, subsequent to the mixture of digestive enzymes and lysosomal hydrolases. Chronic pancreatitis may also involve premature digestive enzyme activation by lysosomal enzymes, as evidence suggests that lysosomal enzymes and activated digestive enzymes may be released from acinar cells during this disease. Further studies will, of course, be needed to confirm these observations, evaluate their significance, and examine the intriguing possibility that drugs directed at controlling lysosomal enzyme activity may find a place in the prevention and/or treatment of pancreatitis.
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