[Pancreatic stellate cells and chronic alcoholic pancreatitis].

Chronic pancreatitis is a disease often characterized by recurrent episodes of abdominal pain accompanied by progressive pancreatic exocrine and endocrine insufficiency [1] and it sometimes requires multiple hospitalizations. Obstructive jaundice, duodenal stenosis, left-sided portal hypertension, pseudocyst and mass formation, and pancreatic carcinoma may occur as complications of chronic pancreatitis. The disease is frequently the result of chronic alcohol abuse, even if other factors such as genetic alterations, autoimmune disorders, and obstructive disease of the biliary tract and the pancreas may cause the disease [2]. Medical therapy is the treatment of choice for most patients and it is based on substitutive therapy for either exocrine or endocrine insufficiency and on analgesics for pain control. In the presence of intractable pain, surgical management is the main option [3] even if, in recent years, other therapeutic options such as endoscopic therapy [4], thoracoscopic splanchnicectomy [5], and extracorporeal shockwave lithotripsy have been applied in clinical practice [6]. From a pathological point of view, chronic pancreatitis is characterized by irregular sclerosis with destruction and loss of the exocrine parenchyma, and complete replacement of acinar, ductal and endocrine tissue by fibrotic tissue. It has recently been reported that acute alcoholic pancreatitis develops in a pancreas already affected by chronic pancreatitis [7]. In 1982, Watari et al. [8] reported the presence of vitamin A-containing cells in the vitamin A-fed rat pancreas. These were later described and characterized as stellate cells in the rat and the human pancreas [9, 10]. Pancreatic stellate cells are morphologically similar to hepatic stellate cells. They bear long cytoplasmic processes and are situated close to the pancreatic acini. In the quiescent state, these cells contain lipid droplets, store vitamin A and express markers such as desmin, glial fibrillary acidic protein, neural cell adhesion molecule and neurotrophin nerve growth factor just as hepatic stellate cells do. Pancreatic stellate cells contain the enzyme alcohol dehydrogenase [11] and, when activated, they assume a myofibroblast-like phenotype [12]. Activated pancreatic stellate cells are characterized by the disappearance of fat globules and the expression of alpha-smooth muscle actin. These cells have proliferative and migratory [13, 14, 15] functions and they also synthesize and secrete extracellular fibrous tissue matrix proteins, matrix metalloproteinases and their inhibitors [16]; it has also been demonstrated that pancreatic stellate cells have phagocytic activity [17]. Thus, the ability of pancreatic stellate cells to synthesize as well as to degrade extracellular matrix proteins suggests their role in …