Acinar Cell Events Initiating Acute Pancreatitis

Pancreatitis is a potentially fatal disease of the exocrine pancreas and one of the most common reasons for hospital admissions for those with GI disease [1–5]. The etiology of human pancreatitis includes gallstones, alcohol abuse, and the effect of various genetic abnormalities. There are two major forms of the disease, acute and chronic [1–11]. Signature responses of acute pancreatitis (AP) include (Fig. 1) the following: increased serum amylase, the inappropriate/premature activation of digestive enzymes within acinar cells (in particular, trypsinogen conversion to trypsin), immune cell infiltration into the pancreas, and acinar cell death [1–3, 6–11]. Recurrent acute pancreatitis is defined as two or more attacks of acute pancreatitis without any evidence of underlying chronic pancreatitis. The key pathologic features of chronic pancreatitis (CP) are progressive loss of acinar tissue, chronic (macrophage-driven) inflammation, and fibrosis [6, 7, 10], ultimately leading to loss of exocrine as well as endocrine pancreatic function (Fig. 1). It is believed that chronic pancreatitis results from repetitive subclinical or clinically evident bouts of AP. Not only is CP associated with poor quality of life, but it is also a major risk factor for pancreatic cancer [12, 13]. Despite decades of intensive research, the pathogenesis of AP remains obscure, and no effective or specific treatment is available [1–5, 10, 11]. This is primarily because of our inadequate knowledge of the molecular and cellular processes initiating and driving the disease.